Malignant mesothelioma in construction workers: the Apulia regional mesothelioma register, Southern Italy.

OBJECTIVE: Asbestos was widely used in construction in both a friable and a compact form until the 1990s, before its use was banned. Today, many of these materials are still in situ and represent a source of risk for construction workers. The objective of the study was to analyse the cases of mesothelioma arising among construction workers registered in the Apulia regional register of mesothelioma. RESULTS: For the period 1993-2018, there were 178 male cases, and 10.2% of the cases were present in the regional register. The average age at diagnosis was 64.7 years. The site was pleural in 96.06% of cases, with a diagnosis of certainty in 86.5% of the total cases and 61.8% of cases with epithelial histology. The average latency is 43.9 years. In 75.2% of cases, the exposure began between 1941 and 1970, with an average duration of 24.3 years. The age at the start of exposure in 68.5% of cases is between 8 and 20 years. The ORs were 2.5 (C.I. 95% 1.01-6.17) for the epithelioid histotype and the high duration of exposure. The data underline the need for prevention and information on all activities involving construction workers in which asbestos-containing materials are still used.

Healthy Diet and Reduction of Chronic Disease Risks of Night Shift Workers.

BACKGROUND: The large increase in epidemiological studies on night shift work is due to the important effects of night shift work on workers' health and psychophysical wellbeing. The short-term effects-insomnia, difficulties in managing work and private life, lower work performance, and more work and extra-work accidents-are easily studied. However, there are several long-term effects that are difficult to study because of the need for detailed exposure assessment and the long latency periods of these diseases. OBJECTIVE: The aim was to collect epidemiologic evidence of diseases in night shift workers, describing their biological pathways and a set of dietary guidelines. METHODS: This is a review on diet and health effects in night shift workers. RESULTS: Significant increases in the rate ratios and hazard ratios of different diseases were associated with modified eating behaviours and poor eating habits among night shift workers. Night shift work is a risk factor for disruption of the circadian rhythms and for some genetic deregulation because it produces the inversion of the sleep/wake cycle and modifies the alternation between activity and rest. CONCLUSION: A healthy diet and improved dietary practices, together with other factors, can reduce shift workers' chronic disease risk. The literature showed the importance of eating behaviour in order to prevent diseases in these workers; therefore, educational programmes are necessary to encourage several important lifestyle changes. The target of our future research will be the role of food components in some dietetic habits for the prevention of disease in night shift workers.

Urine chemokines: biomarkers of human lupus nephritis?

Lupus nephritis is characterized by intrarenal inflammation. Leukocytes trafficking from peripheral blood into affected tissues spaces represent an important factor in the development of many renal diseases. During the past few years has been attributed the crucial role of a family of chemotactic cytokines--the chemokines--in this process. In the course of renal diseases, the infiltration of monocytes/macrophages and T cells into kidneys represent an important role in progressive interstitial fibrosis and the progression of chronic renal failure. In this review, we summarize the in vitro and in vivo data on chemokines and chemokine receptors in kidney diseases, with a special focus on urine chemokine measurement as possible biomarker of human lupus nephritis.

[Molecular epidemiology in occupational medicine: methodological features and impact of individual genetic susceptibility]. / Epidemiologia molecolare in medicina del lavoro: aspetti metodologici e influenza della suscettibilità genetica individuale.

A review of main methodological questions regarding biomarkers is reported focusing on validation, laboratory variability, study design and statistical analysis. The indicated perspective is the setup of protocols finalized at the study of multiple panels of genotoxicity biomarkers taking into account the influence of gene-environment interaction at low doses, of the modulation of the biomarkers associated to the genetic polymorphism. An overview on the influence of metabolic and DNA repair polymorphisms on biological indicators of genotoxic risk in occupational, environmental or life-style exposure is also presented. Genetic polymorphisms that influence human genotoxic risk are those of glutathione s-transferase and cytochrome P450 in exposure to polycyclic aromatic hydrocarbons (PAHs), those of N-acetyltransferase in both occupational and environmental exposures to aromatic amines (AAs) and similar compounds. Lastly recent and important studies, on the effect of the newly discovered polymorphisms affecting DNA repair enzymes on the modulation of genotoxic risk linked to life style (i.e., aflatoxin and PAHs from diet) and smoking behaviour and to environmental genotoxic exposure, are reported. To date biomarkers represent a new tool for epidemiological research in occupational medicine and they could represent a valid instrument for group evaluation but they are not useful for the risk assessment on individual basis. To achieve this objective it is necessary to demonstrate a stronger association with the endpoint that perhaps the future development of genetic and molecular epidemiology will make possible.

[Exposure to PAHs, urinary 1-pyrenol and DNA adducts in samples from a population living at different distances from a steel plant]. / Esposizione a IPA, 1-idrossipirene urinario e addotti al DNA in campioni di popolazione residenti a diversa distanza da un polo siderurgico.

This study aims at measuring association between environmental exposure to PAHs and internal or biologically effective dose biomarkers among 212 individuals living at different distance from the industrial area of Taranto, Italy. Environmental PAH exposure was determined by area monitoring. PAH levels was measured by HPLC UV/FL. Urinary 1-hydroxypyrene levels were measured by HPLC/Fluorescence. The levels of DNA adducts were determined by 32P. post-labelling. A questionnaire was administered to gather personal data, residence, occupational history, alcohol, tobacco smoke, and diet, to control for other sources of exposure to PAH. Blood and urinary samples, drawn from the subjects studied were collected and analysed. A multivariate regression model was used to investigate the influence of several confounding factors. Housing was placed within 1 km from smokestacks in Taranto and Statte, whereas they were more far away in Locorotondo and in Alberobello. The prevalence of current smokers was 31.6%.

Anti-neutrophil cytoplasmic antibodies in echinococcus granulosus hydatid disease.

The authors studied the presence of ANCA, evaluated by indirect immunofluorescence (IIF) and ELISA for anti-lactoferrin (LF), and anti-myeloperoxidase antibodies (anti-MPO), in sera of 69 patients with cystic echinococcosis (CE). According to Caremani's classification, 27 patients were considered to have active cysts and 42 patients were considered to have inactive cysts. ANCA were detected in 9 out of 27 patients (33.3%) with active cysts and in 3 out of 42 patients (7.1%) with inactive cysts. Differences between the two groups were statistically significant (P < 0.05). Anti-LF antibodies were found in seven patients (10.14%) and anti-MPO antibodies in ten patients (14.5%).

Assessment of echocardiographic abnormalities in patients with systemic lupus erythematosus: correlation with levels of antiphospholipid antibodies.

BACKGROUND: The aim of this study was to evaluate the incidence of morphologic and functional cardiac abnormalities in patients with systemic lupus erythematosus and correlate the data with antiphospholipid antibody (aPL) levels. METHODS: Ninety-one patients with systemic lupus erythematosus were enrolled and divided into two groups according to the presence (Group 1, n = 45) or absence of aPL (Group 2, n = 46). All patients underwent standard two-dimensional and Doppler echocardiographic examination. aPL were detected by a standardized and validated ELISA test. Five patients with regional ventricular dysfunction also underwent coronary angiography. The chi2 test was used for the statistical analysis of the data. For smaller groups of samples the Fisher's exact test was employed. RESULTS: Pericardial effusion was detected in 19 patients without any statistical difference between the two groups. A valvular involvement was present in 39 patients: a moderate-severe degree was more frequent in Group 1 (p = 0.02). Regional wall motion abnormalities were observed in 8 patients: only 1 in Group 2 and 7 in Group 1 (p = 0.03). Coronary angiography showed normal arteries in all patients of Group 1. CONCLUSIONS: aPL play a role in the pathogenesis of the severity of valvular lesions as well as in regional myocardial dysfunction, suggesting a small vessel disease.

Increased levels of lactoferrin in synovial fluid but not in serum from patients with rheumatoid arthritis.

Lactoferrin is a multifunctional immunoregulatory protein, stored in specific granules of neutrophil granulocytes, from which it is released following cell activation. As activated neutrophils play a crucial role in the destruction of synovial joints in rheumatoid arthritis, we evaluated lactoferrin concentration in synovial fluid and sera from 21 patients with rheumatoid arthritis and 11 patients with osteoarthritis. We also measured lactoferrin levels in sera from 12 healthy controls. Lactoferrin was measured by a solid-phase inhibition immunoassay. Median lactoferrin levels were significantly higher in synovial fluid from rheumatoid arthritis than from osteoarthritis patients (P = 0.0002). In contrast, no significant difference was found between serum lactoferrin from patients with rheumatoid arthritis or osteoarthritis compared with normal controls. In patients with rheumatoid arthritis, lactoferrin concentrations were higher in synovial fluid than in sera (P = 0.036). In both rheumatoid arthritis and osteoarthritis no correlation was found between serum and synovial fluid lactoferrin (P = 0.51 and P = 0.5, respectively). In synovial fluid from patients with rheumatoid arthritis, lactoferrin concentrations correlated with neutrophil granulocyte count (P < 0.0001), but neither serum nor synovial lactoferrin levels correlated with disease activity (P = 0.32 and P = 0.25, respectively). In conclusion, lactoferrin is a reliable marker of neutrophil activation at sites of inflammation in rheumatoid synovitis, but does not represent a marker of disease activity.

The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers.

The present study has the aim of evaluating gene-environment interaction on the levels of different biomarkers in coke-oven workers exposed to PAH. In order to assess whether the levels of some biomarkers (PAH-DNA adducts, nitro-PAH adducts to Hb and MN frequency) could be modulated by the genetic metabolic polymorphisms for CYP1A1 and GSTM1, we analysed in 76 coke-oven workers and 18 controls the CYP1A1 (MspI and Ile/Val sites) and the GSTM1 genotypes by a PCR assay. In individuals with shared setup of CYP1A1 or GSTM1 genotypes, we analysed how the specified biomarkers correlated with total PAH exposure (urinary levels of 1-hydroxypyrene) both by a stratified analysis and logistic regression modelling. Statistically significant (P = 0.03 and P = 0.01) higher percentages of the more susceptible GSTM1- subjects compared to the GSTM1+ subjects and of the more susceptible CYP1A1 Ile/Val individuals compared to the CYP1A1 Ile/Ile individuals were detected for high levels of PAH-DNA adducts in the high exposure group (namely high levels of 1-OHP). A statistically significant association was observed between increased PAH-DNA adduct levels and the more susceptible GSTM1- genotype (P.O.R. = 4.18, P = 0.03) in a logistic regression modelling and a significant interaction between PAH exposure and GSTM1-genotype was found for PAH-DNA adducts. No effect of these metabolic genotypes was observed for MN frequency and nitro-PAH adducts to Hb. In conclusion, a gene-environment interaction between PAH exposure and two metabolic genotypes involved in activation (CYP1A1) and detoxification (GSTM1) of PAHs, respectively, has been identified.

Neurological involvement in antiphospholipid antibodies syndrome (APS).

Antiphospholipid antibodies (aPL) have been most strongly associated with a syndrome (APS) characterized by venous and/or arterial thrombosis, thrombocytopenia, recurrent fetal losses and a variety of non-thrombotic and thrombotic neurological disorders. Cerebral ischemia associated with aPL is the most common arterial thrombotic manifestation. Other neurological syndromes, such as cognitive dysfunction, dementia, psychosis, depression, seizures, chorea and transverse myelopathy, have all been associated with antiphospholipid antibodies.

Methimazole treatment in Graves' disease: behaviour of CD5+B lymphocytes and regulatory T cell subsets.

In the present study we analyzed some circulating lymphocyte subsets in eleven patients affected by Graves' disease before and after three and six months of methimazole treatment. Peripheral blood mononuclear cells were studied by a panel of monoclonal antibodies with single and double fluorescence cytometric analysis. Our results demonstrated an increased percentage of CD5+B cells and HLADR+T lymphocytes at the beginning of the disease in comparison to the normal controls (p < 0.001), and a significant decrease after six months of treatment (p < 0.01 and p < 0.05, respectively). The CD4+ CD45RA+ subset was significantly reduced in untreated Graves' patients in comparison to the normal group (p < 0.01), and increased towards normalization after six months of treatment. The significant modifications of lymphocyte subsets, as well as the reduction of thyroid autoantibodies, support a direct or mediated effect of methimazole on the immune system.

Pathophysiology, clinical features and management of hepatorenal syndrome.

Hepatorenal syndrome (HRS) is a form of functional renal failure occurring in patients with advanced liver disease. Hypoperfusion of the kidney, due to renal vasoconstriction, is the main feature of HRS. Conversely, the extrarenal circulation is characterized by low systemic resistance, especially occurring in splanchnic vessels, and arterial hypotension. It has been postulated that renal vasoconstriction is induced either by a hepatorenal reflex related to the diseased liver or by arterial vasodilation and the subsequent baroreceptor-mediator activation of systemic vasoconstrictor factors. The diagnosis of HRS requires the exclusion of other causes of renal failure in patients with liver disease. On the basis of clinical and prognostic differences, two types of HRS have been defined. The prognosis of HRS is poor and, to date, the only effective treatment is the liver transplantation.

Expression of lactoferrin on human granulocytes: analysis with polyclonal and monoclonal antibodies.

Lactoferrin (LF), an iron-binding protein present in specific granules of neutrophils, is expressed on membrane after granulocyte activation. It may represent a target for anti-neutrophil cytoplasmic antibodies (ANCA) in patients affected by some immunomediated diseases. We recently produced two MoAbs, AGM 2.29 and AGM 10.14, that recognize two spatially distant epitopes of human LF. In this study we perform a cytometric analysis in order to evaluate the expression of LF on the surface of granulocytes obtained from freshly drawn blood or after purification, in both the presence and absence of stimuli. Our results demonstrate that LF is not constitutively expressed on membrane of circulating neutrophils. After priming with phorbol myristate acetate (PMA) or tumour necrosis factor-alpha (TNF-alpha), an increased mean fluorescence intensity (MFI) was obtained on neutrophils stained with polyclonal anti-LF antibodies and with AGM 2.29. The kinetics of LF expression during activation demonstrated a progressive increase in MFI within 45 min. No increase in MFI was documented when primed granulocytes were stained with MoAb AGM 10.14, thus indicating that the epitope recognized by AGM 10.14 is not exposed at the cell surface. Following membrane permeabilization, performed in order to analyse the binding of anti-LF MoAbs to cytoplasmic LF, a marked increase in MFI was obtained by staining granulocytes with both anti-LF MoAbs. Indirect immunofluorescence (IIF) analysis confirmed that AGM 2.29 and AGM 10.14 reacted with human granulocytes, showing a cytoplasmic pattern on formalin-acetone-fixed neutrophils and a perinuclear one on ethanol-fixed cells.

Anti-TNF-alpha antibodies are not associated with Helicobacter pylori induced gastritis.

Over the past few years, it has been suggested that increased gastric production of some cytokines, including tumor factor-alpha (TNF-alpha), play a crucial role in the pathogenesis of H. pylori associated gastroduodenal diseases. On the other hand, it has been postulated that the presence of autoantibodies directed against several cytokines could represent or a down-regulatory response of the host to limit the damage associated with chronic bacterial infection or a specific cytokine inhibitor. The aim of this study was to evaluate whether serum anti-TNF-alpha antibodies are produced in response to H. pylori infection. The anti-TNF-alpha antibody titer among H. pylori positive and H. pylori negative patients showed no statistically significant difference. Interestingly, after eradication of H. pylori, no significant modification in anti-TNF-alpha antibody levels was found. In H. pylori positive patients, no correlations (either positive or negative) was demonstrated between anti-TNF-alpha antibody and activity of gastritis, nor between these antibodies levels and presence of duodenal ulcer. The lack of correlation between anti-TNF-alpha antibody levels and activity of gastritis indicates that these autoantibodies do not affect the clinical course of the H. pylori associated gastroduodenal diseases. Therefore, the biological and clinical relevance (if any) of anti-TNF-alpha antibodies in H. pylori associated gastritis remains to be better elucidated.

CD5 B cells in autoimmune and non immune-mediated thyroid dysfunctions.

In a previous study we demonstrated a significant increase of CD5+ B subset in patients with Graves' disease (GD) compared with normal controls. The aim of this study was to compare the percentage of CD5+ B and CD5- B cells in GD with that in different forms of autoimmune and non immune-mediated thyroid diseases. Seventy-two patients were studied: 28 patients with GD, 20 with silent thyroiditis (ST), 12 with Hashimoto's disease (HD), and 12 subjects affected by hyperthyroidism due to toxic adenoma (TA). Eleven out of 28 patients with GD were also evaluated after six months of methimazole treatment. The study was performed by cytometric analysis. In GD the percentage and the absolute number of CD5+ B cells were significantly increased compared with normal controls (42.5 +/- 18.2% versus 19 +/- 6.3%, p < 0.0001; 142 +/- 153.3/cmm versus 46.9 +/- 22/cmm, p < 0.003, respectively. CD5+ B cells tended to normalise after six months of treatment. In ST the percentage of CD5+ B cells was increased (28.6 +/- 10.2%); conversely the absolute number was in the normal range. Patients affected by HD did not show any significant modification in B cells and their subsets in comparison with controls. In TA, CD5+ B were 7.6 /- 4.4% and 14.3 /- 10.9/cmm. Our results demonstrated a marked increase in both percentage and absolute number of CD5+ cells, only in active GD. The expansion of CD5+ B cells could play a role in the immune imbalance present in this disease.

Long-term treatment of systemic lupus erythematosus with cyclosporin A.

OBJECTIVE: To evaluate the efficacy of long-term treatment with cyclosporin A (CSA) in systemic lupus erythematosus (SLE). METHODS: Thirty patients with SLE whose condition was either poorly responsive or unresponsive to treatment with steroids and/or cytotoxic drugs were enrolled in a prospective, nonrandomized study of CSA. Patients with hypertension or hypercreatinemia were excluded. Disease activity was evaluated according to the systemic lupus activity measure. Assessments were made prior to study entry and after 6, 12, 18, and 24 months. RESULTS: Twenty-seven patients completed at least 24 months of treatment with CSA. The mean disease activity score significantly decreased after 6 months of therapy (P < 0.01); this result was maintained throughout the study. A conspicuous steroid-sparing effect was observed following administration of CSA (P < 0.01). Side effects included hypertrichosis (63% of patients), paresthesias (23%), gastrointestinal symptoms (20%), gingival hyperplasia (17%), hypertension (10%), tremors (7%), and nephrotoxicity (13%). No significant changes in serum creatinine levels were observed. CONCLUSION: CSA represents a helpful second-choice treatment for patients with active SLE. Administration of CSA necessitates expert and careful followup of patients.

Coexpression of CD69 and HLADR activation markers on synovial fluid T lymphocytes of patients affected by rheumatoid arthritis: a three-colour cytometric analysis.

The aim of the present study was to evaluate the coexpression of very early (CD69), early (CD25) and late (HLADR) antigens and to analyse the mean fluorescence intensity (MFI) of such activation markers on synovial fluid (SF) and peripheral blood (PB) lymphocytes of patients affected by rheumatoid arthritis (RA) and other types of chronic synovitis (OCS). A three colour cytometric analysis was performed using a peridinin chlorophyll protein conjugated anti-CD3 antibody in combination with fluorescein isothiocyanate or phycoerythrin labelled anti-CD69, anti-HLADR, anti-CD25 monoclonal antibodies (mAbs). A T cell gating method was utilized, so that three sets of bivariant dot plot quadrant displays were obtained (CD69/HLADR, CD69/CD25, CD25/HLADR). A large percentage of SF T lymphocytes in RA showed the coexpression of very early and late activation antigens (CD3 + CD69 + HLADR +), whereas CD3 + CD69 + CD25 + bearing cells and CD3 + CD25 + HLADR + lymphocytes were only a small percentage. Similar results were obtained in patients with OCS, although to a lesser extent. No statistically significant differences in MFI of CD69 and HLADR positive SF T cells between RA and OCS were observed. The CD69 + CD25-HLADR + T cell subset is the most commonly represented in the synovial environment, among those we have evaluated; this phenotype may be characteristic of chronic inflammatory arthritis.

Two spatially distant epitopes of human lactoferrin.

Lactoferrin (LF) is an iron binding protein, which may represent a target for antineutrophil cytoplasmic antibodies (ANCA) in patients affected by rheumatoid arthritis, ulcerative colitis, and primary sclerosing cholangitis. Here we describe the production and characterization of two new monoclonal antibodies (MAbs) against human LF. These MAbs (AGM 10.14, an IgG1, and AGM 2.29, an IgG2b) recognize spatially distant epitopes of LF as assessed by cross-blocking experiments. We also demonstrated by indirect immunofluorescence that both MAbs react with ethanol-fixed neutrophil granulocytes showing a perinuclear staining pattern. AGM 2.29 and AGM 10.14 have been utilized as capture and labeled tracer antibody, respectively, in a double determinant immunoassay (DDIA) to measure soluble LF. The results obtained show that this DDIA allows us to quantify even low concentrations of LF, the maximal range of the assay sensitivity being between 12 and 780 ng/ml. Therefore, AGM 10.14 and AGM 2.29 may represent useful reagents for studying the role of autoantibodies to LF as well as for measuring soluble LF, which is a reliable secretory marker of neutrophil activation.

Hypertension and menopausal syndrome: effects of hormone replacement therapy and antihypertensive drugs.

Arterial hypertension is a common finding in climacteric women even though the role of reduced estrogen levels in promoting this condition remains unclear. The purpose of the present survey was to evaluate the effects of hormone replacement therapy in hypertensive postmenopausal women. 180 patients were studied; they had been postmenopausal for 12-18 months and afflicted with mild or moderate essential arterial hypertension for less than 2 years. Patients were randomly divided into two groups and treated with progestin-estrogen therapy (group I, 96 patients) or with antihypertensive drugs (group II, 84 patients). Fourty-one cases in group I (42.7%) responded adequately to hormone therapy with persistent normalization of blood pressure levels; antihypertensive drugs were effective in 61 patients in group II (72.5%). The 23 unresponsive patients in group II were subsequently treated with progestin-estrogen therapy and a normalization of pressure values was achieved in 10 of these (43.5%). These results suggest that hormonal treatment determines, in at least one third of the cases, a significant reduction in blood pressure values. Moreover, hormone replacement may be effective even in patients that have not responded to antihypertensive drugs.