Composition and origin of PM2.5 in Mediterranean Countryside.

In this work PM2.5 was collected during winter and summer in a Sardinian village (Gonnostramatza, Italy) highly affected by biomass burning emissions. A multi-technique approach was adopted for the complete PM chemical characterization. The bulk characterization was performed by IC (Ion Chromatography), HPAEC (High-Performance Anion-Exchange Chromatography), TOT (Thermal Optical Transmittance) and ED-XRF (Energy-Dispersive X-Ray Fluorescence) while XPS (X-ray Photoelectron Spectroscopy) was used for the surface characterization. Using levoglucosan as specific tracer of biomass burning emissions, the assessment of the impact of this source was carried out and it represent the major PM source at the investigate site during winter. In winter the average levoglucosan concentration is 2096 ±â€¯324 ng/m3 while during summer its concentration is negligible (18 ±â€¯7 ng/m3). Levoglucosan content in PM2.5 during winter is on average 13.7%; it is estimated that 65% of PM2.5 is due to wood burning. XPS has been exploited in this work aiming at highlighting possible differences between surface and bulk composition of PM2.5. The surface of the particulate matter resulted enriched in carbon compared to the bulk. Among the components of XPS C1s signals recorded on the samples collected during winter, it was found that the signal at 286.5 eV, which is due to the presence of COH, reflects the bulk composition of levoglucosan.

Oral health sentinel-based surveillance: a pilot study on dentinal hypersensitivity pain.

Aim of the study is to assess the development of a structured sentinel system for oral health data collection at national level. Furthermore, this pilot study aims to investigate the prevalence data on dentinal sensitivity pain collected through a nationwide network of epidemiological sentinels (dental hygienists). Each sentinel was given a specific number of examinees and periodicity of data collection. Overall, 116 adults were recruited from 19 Regions, 42,24% male and 57,76% female, with a mean age of 26. DH result was consistent with literature data, being 45%. All sentinel completed the standard forms and assured a good compliance. The overall good customer satisfaction assures adhesion of the sentinels to the procedure, and the regular data collection. The pilot study proved the effectiveness of a structured nationwide network of epidemiological sentinels (dental hygienists) for oral health data collection at national level. This methodology can be an essential starting point for periodic comparative studies.

Exploring the potential of gold(III) cyclometallated compounds as cytotoxic agents: variations on the C

A series of novel (C^N) cyclometallated Au(III) complexes of general formula [Au(py(b)-H)L(1)L(2)](n+) (py(b)-H = C^N cyclometallated 2-benzylpyridine, L(1) and L(2) being chlorido, phosphane or glucosethiolato ligands, n = 0 or 1) have been synthesized and fully characterized using different techniques, including NMR, IR and far-IR, mass spectrometry, as well as elemental analysis. The crystal structure of one compound has been solved using X-ray diffraction methods. All compounds were tested in vitro in five human cancer cell lines including the lung, breast, colon and ovarian cancer cells. For comparison purposes, all compounds were also tested in a model of healthy human cells from the embryonic kidney. Notably, all new compounds were more toxic than their cyclometallated precursor bearing two chlorido ligands, and the derivative bearing one phosphane ligand presented the most promising toxicity profile in our in vitro screening, displaying a p53 dependent activity in colorectal cancer HCT116 cells. Finally, for the first time C^N cyclometallated gold(III) complexes were shown to be potent inhibitors of the zinc finger protein PARP-1, involved in the mechanism of cisplatin resistance.

Effect of Fluoridated Sealants on Adjacent Tooth Surfaces: A 30-mo Randomized Clinical Trial.

A double-blind randomized clinical trial was performed in 6- to 7-yr-old schoolchildren to evaluate, in a 30-mo period, whether the caries increment on the distal surface of the second primary molars adjacent to permanent first molars sealed with fluoride release compounds would be lower with respect to those adjacent to permanent first molars sealed with a nonfluoridated sealant. In sum, 2,776 subjects were enrolled and randomly divided into 3 groups receiving sealants on sound first molars: high-viscosity glass ionomer cement (GIC group); resin-based sealant with fluoride (fluoride-RB group); and a resin-based sealant without fluoride (RB group). Caries (D1 - D3 level) was recorded on the distal surface of the second primary molar, considered the unit of analysis including only sound surfaces at the baseline. At baseline, no differences in caries prevalence were recorded in the 3 groups regarding the considered surfaces. At follow-up, the prevalence of an affected unit of analysis was statistically lower (p = .03) in the GIC and fluoride-RB groups (p = .04). In the GIC group, fewer new caries were observed in the unit of analysis respect to the other 2 groups. Incidence rate ratios (IRRs) were 0.70 (95% confidence interval: 0.50, 0.86; p < .01) for GIC vs. RB and 0.79 (95% confidence interval: 0.67, 0.89; p = .005) for fluoride-RB vs. RB [Corrected]. Caries incidence was significantly associated with low socioeconomic status (IRR = 1.18; 95% confidence interval: 1.10, 1.42; p = .05). Dental sealant high-viscosity GIC and fluoride-RB demonstrated protection against dental caries, and there was evidence that these materials afforded additional protection for the tooth nearest to the sealed tooth (clinical trial registration NCT01588210).

Fluoride concentration from dental sealants: a randomized clinical trial.

A randomized clinical trial was performed in schoolchildren (6-7 yrs) to evaluate fluoride concentration in interproximal fluid after the placement of 3 different sealants. The sample consisted of 2,776 children randomly divided: 926 in the high-viscosity Glass-ionomer Cement group (GIC group), 923 in the fluoride Resin-based group (fluoride-RB group), and 927 in the no-fluoride Resin-based group (RB group). In total, 2,640 children completed the trial. Sealants were applied following manufacturer's instructions. Interproximal fluid samples were collected at baseline and 2, 7, and 21 days after application of sealants, by insertion of a standardized paperpoint into the interproximal mesial space of the sealed tooth for 15 seconds. Fluoride concentration was evaluated by means of a fluoride ion-selective electrode. At 2 days after sealant application, fluoride concentration was significantly higher in GIC and fluoride-RB groups compared with that in the RB group (p < .01). Mean fluoride concentrations after 7 days were 2.54 (SE 0.68) ppm, 0.85 (SE 0.26) ppm, and 0.53 (SE 0.11) ppm for the three groups, respectively. After 21 days, fluoride concentration in the GIC group remained higher than that in the other two groups. High-viscosity GIC sealants increased the fluoride concentrations in interproximal fluid more than did a Resin-based sealant containing fluoride.

Effect of a sugar-free chewing gum containing magnolia bark extract on different variables related to caries and gingivitis: a randomized controlled intervention trial.

The effect of magnolia bark extract (MBE) on different variables related to caries and gingivitis administered daily through a sugar-free chewing gum was evaluated. The study was performed with healthy adult volunteers at high risk for caries as a randomized double-blind interventional study. 120 subjects with a salivary mutans streptococci (MS) concentration ≥10(5) CFU/ml and presence of bleeding on probing >25% were enrolled and divided into three groups: magnolia, xylitol and control. The study design included examinations at baseline, after 7 days, after 30 days of gum use and 7 days after the end of gum use. Plaque pH was assessed using the strip method following a sucrose challenge. Area under the curve (AUC(5.7) and AUC(6.2)) was recorded. Whole saliva was collected and the number of salivary MS (CFU/ml) was counted. Bleeding on probing was recorded as a proxy of dental plaque. Data were analyzed using ANOVA repeated measures. Magnolia gum significantly reduced plaque acidogenicity, MS salivary concentration and gingival bleeding compared to xylitol and control gums. Subjects from the magnolia and xylitol groups showed both MS concentration (p = 0.01 and 0.06, respectively) and AUC(5.7) (p = 0.01 and 0.04, respectively) to be significantly lower compared to baseline. Thirty-day use of a chewing gum containing MBE showed beneficial effects on oral health, including reduction of salivary MS, plaque acidogenicity and bleeding on probing.

Conceptual basis and methodology of the SOPHIA study.

To clarify the role of gene polymorphisms on the effect of losartan and losartan plus hydrochlorothiazide on blood pressure (primary end point) and on cardiac, vascular and metabolic phenotypes (secondary end point) after 4, 8, 12, 16 and 48 weeks treatment, an Italian collaborative study - The Study of the Pharmacogenomics in Italian hypertensive patients treated with the Angiotensin receptor blocker losartan (SOPHIA) - on never-treated essential hypertensives (n = 800) was planned. After an 8 week run-in, losartan 50 mg once daily will be given and doubled to 100 mg at week +4 if blood pressure is more than 140/90 mmHg. Hydroclorothiazide 25 mg once daily at week +8 and amlodipine 5 mg at week +16 will be added if blood pressure is more than 140/90 mmHg. Cardiac mass (echocardiography), carotid intima-media thickness, 24 h ambulatory blood pressure, homeostatic model assessment (HOMA) index, microalbuminuria, plasma renin activity and aldosterone, endogenous lithium clearance, brain natriuretic peptide and losartan metabolites will be evaluated. Genes of the renin-angiotensin-aldosterone system, salt sensitivity, the beta-adrenergic system and losartan metabolism will be studied (Illumina custom arrays). A whole-genome scan will also be performed in half of the study cohort (1M array, Illumina 500 GX beadstation).

Fifteen-year follow-up of thyroid function in lithium patients.

OBJECTIVE: To study prospectively the course of clinically relevant thyroid dysfunction in a cohort of patients on long-term lithium treatment. METHOD: Patients (no.=150) who had undergone a cross-sectional evaluation of their thyroid function in 1989, when they were at different stages of lithium treatment, were followed up for thyroid circulating thyroid antibodies, hypothyroidism, hyperthyroidism, and thyroidectomy, during a further period of lithium exposure of up to 15 yr. RESULTS: Annual rates of newly developed circulating thyroid antibodies and hypothyroidism were 1.7 and 1.5%, respectively. Subjects with thyroid antibodies had a higher chance of requiring substitution treatment with levothyroxine for hypothyroidism compared with subjects with no evidence of thyroid antibodies (6.4% annual rate compared to 0.8%; relative risk: 8.4; 95% confidence interval: 2.9-24.0). One case of hyperthyroidism was observed over 976 patient-yr. Three patients underwent thyroidectomy during followup (two for multinodular goiter and one for multicentric papillary carcinoma). CONCLUSIONS: Lithium may be associated with hypothyroidism in particular in the presence of circulating thyroid antibodies. Incidence of thyroid antibodies is comparable with that reported for the general population. Hyperthyroidism and thyroid cancer are rare.

Comparative acute effects of brimonidine 0.2% versus dorzolamide 2% combined with beta-blockers in glaucoma.

PURPOSE: To assess the acute intraocular hypotensive efficacy of brimonidine tartrate 0.2% (a highly selective alpha2-adrenergic agonist) compared with dorzolamide 2% (a topical carbonic anhydrase inhibitor) as adjunct therapy to topical beta-blockers in patients with primary open-angle glaucoma. METHODS: A randomized cross-over masked study was performed. We enrolled one eye of each of 28 patients who were on different beta-blocker therapy. We measured the intraocular pressure (IOP) 2 h after the beta-blocker instillation; we then randomly administered one of the two drugs and we compiled an IOP diurnal curve. One month later we repeated the same procedures with the second drug. Unpaired Mann-Whitney U-test was used to compare decreases in IOP between the two drugs (P<0.05). RESULTS: Both brimonidine 0.2% and dorzolamide 2% have good ocular hypotensive efficacy, significantly lowering IOP when compared to beta-blocker therapy alone, for the whole diurnal curve. Maximum mean percent IOP decrease from baseline was 22.0+/-15.7% (4.0+/-2.9 mmHg) for dorzolamide 2% 6 h after instillation and 35.5+/-16.4% (7.0+/-4.1 mmHg) for brimonidine 0.2% 8 h after administration of the drug. When we compared the two treatments, brimonidine 0.2% showed a higher hypotensive effect than 2% dorzolamide after 4 h (28.4+/-16.8% vs 17.6 +/-9.3%; P=0.04) and 8 h (35.5+/-16.4% vs 21.6 +/-10.8%; P=0.04). CONCLUSION: This study indicates that 0.2% brimonidine acutely associated with beta-blockers is an interesting new combination treatment useful in the management of glaucoma.

Focal electroretinograms and fundus appearance in nonexudative age-related macular degeneration. Quantitative relationship between retinal morphology and function.

BACKGROUND: The aim of this study was to evaluate the focal electroretinogram (FERG), an objective indicator of outer retinal function, in nonexudative age-related macular degeneration (NE-AMD), and to compare FERG results with morphological lesions assessed by stereoscopic fundus photographs and fluorescein angiograms. METHODS: Twenty-five patients (25 eyes) with bilateral NE-AMD (visual acuity of the study eyes > or = 0.4) as well as 10 age- and sex-matched control subjects (10 eyes) were evaluated. FERGs were recorded from the macular region (9 degrees) in response to sinusoidal stimuli flickered at 32 Hz. Amplitude and phase angle of the Fourier-analyzed FERG fundamental component were measured. Fundus lesions were graded from color slides according to the Wisconsin age-related maculopathy grading system . Fluorescein angiograms were evaluated by an image analysis technique to compute the area with pathological hyperfluorescence (associated with drusen and/or retinal pigment epithelial atrophy) within the macular (approximately 9 degrees x 9 degrees) region. RESULTS: Compared to control eyes, NE-AMD eyes had a reduction in the mean FERG amplitude (57% loss, P<0.001) with no phase changes. Amplitudes of individual affected eyes were negatively correlated with either the Wisconsin grading score (r = -0.63, P < 0.001) or the percentage area of pathological hyperfluorescence (r = -0.70, P<0.01). Eyes with minimal NE-AMD lesions (Wisconsin score < or = 6) and normal acuity had a lower mean amplitude (47% loss, P < 0.05) than that of control eyes. CONCLUSIONS: The results indicate that, in NE-AMD, the FERG is altered in parallel with the extent and severity of fundus lesions. However, a functional impairment of outer macular layers, which is detected by FERG losses, could precede morphological changes typical of more advanced disease.

[Prosopagnosia. Description and discussion of a clinical case]. / Prosopagnosia. Descrizione e discussione di un caso clinico.

Prosopagnosia was due to a right occipito-temporal infarct, but clinical and computed tomographic features emphasized a previous symmetrical damage in the left side. The case reported, and especially elaboration of literature data relative to this peculiar type of visual agnosia, suggest that bilaterality of cerebral lesions in the determining factor of prosopagnosia.

Comparison of sublingual and oral captopril in hypertension.

The use of sublingual captopril has been recently suggested in hypertensive crisis on the assumption of a faster absorption and thus a more rapid effect on blood pressure than with the oral route. To verify this hypothesis we have compared the hypotensive effect of oral and sublingual captopril in 40 essential hypertensives who were randomly allocated to either route of administration. Captopril was administered orally dissolved in water or allowed to dissolve under the tongue. After 5, 10, 20, 30, 40, 60 and 90 minutes blood pressure, Plasma Renin Activity (PRA) and Angiotensin Converting Enzyme (ACE) were measured. No significant differences were found between the two groups in the time course of blood pressure decrease, PRA increase and ACE inhibition. The changes of the parameters studied was superimposable irrespective of the route of administration thus not supporting the hypothesis that sublingual captopril might be absorbed more rapidly.

Immunoradiometric assay of active renin in human plasma: comparison with plasma renin activity.

The direct measurement of active renin with monoclonal antibodies (IRMA) in plasma from hypertensive patients was compared with the traditional PRA method. Two monoclonal antibodies were used: 3E8 and 4G1. The first was coupled to magnetizable beads and was used to trap both active and inactive renin from plasma. The second antibody, 4G1, was iodinated and used to detect active renin trapped by 3E8. The correlation coefficient between the two methods was very high (r = 0.98, p less than 0.001) in plasma samples whose PRA values were higher than 2 ng/ml/h; in low renin samples (PRA lower than 2 ng/ml/h) no significant correlation was found (r = 0.12 n.s.). When PRA and IRMA were performed before and after trypsin activation of inactive renin, the percentage of inactive over total renin was 86.8% and 84% as calculated with PRA and IRMA respectively. The direct monoclonal antibodies method for measuring active renin can be usefully adopted, in conjunction with the traditional PRA procedure, in studying both clinical and pathophysiological aspects of the renin-angiotensin system.

Double-blind preference and compliance multicentre study in osteoarthritis: once-a-day treatment.

Two-hundred-and-three female patients (mean age: 58 yrs; SD: 8.2 yrs) suffering from osteoarthritis entered this late phase IV multicentre, stratified according to previous therapy (e.g. ketoprofen, naproxen, aspirin, indomethacin or indoprofen), randomized, double-blind, between within-patient trial of 2-week duration. Each patient received either diclofenac SR 100 mg/day (D), piroxicam 20 mg/day (P), or placebo (P1 by oral route. Clinical evaluation (functional class; pain assessment; osteoarthritic condition; joint motility and stiffness) was performed at entry, as well as after the first and the second week. Patient compliance and reported signs and symptoms were recorded after the first week and at the end of the trial. Patient preference, as regards previous therapy, and global evaluation (both by the physicians and the patients) were checked at the end of the trial. The clinical evaluation showed a superiority of D and P over P1. No difference was seen between the two active drugs. Placebo effect was very strong. Global evaluation was significantly in favour of D and P. Patient compliance was extremely good (greater than or equal to 95%). Diclofenac was preferred to naproxen, aspirin and indomethacin, while piroxicam and placebo were preferred only to aspirin. The tolerability of the two active drugs was good and comparable. A significantly lower number of patients complaining of unwanted effects (u.e.) was detected in the placebo group. The number of patients withdrawn for u.e. was similar in the three trial groups.

[Hyperuricemia in essential hypertension. Considerations on some pathogenic aspects]. / L'iperuricemia nell'ipertensione essenziale. Considerazioni su alcuni aspetti patogenetici.

Hyperuricaemia was encountered in 29% of 55 subjects with essential hypertension, who had not been treated with anti-hypertensive drugs, as against a 10% incidence in a group with normal blood pressure. No relationship between hyperuricaemia and level of hypertension was found. The normal glomerular filtration, the frequent reduction in uric acid clearance and its correlation with uricaemia are held to be indicative of a tubular defect in the excretion of uric acid, as a cause of hyperuricaemia. The reduction in renal plasma flow and its significant correlation with uricaemia and uric acid clearance are considered probable causes of reduced renal excretion. In conclusion it is hypothesised that hypertension triggers renal haemodynamic disturbances and hence hyperuricaemia.

Active and inactive renin after a single dose of captopril in hypertensive patients.

In 25 hypertensive patients (15 with renal artery stenosis and 10 with essential hypertension), captopril, in a single 12.5 mg dose, caused a prompt decrease in arterial pressure without changing the heart rate. Plasma active and trypsin-activated renin significantly increases, whereas inactive renin and plasma aldosterone decreased. The plasma active/inactive renin ratio was also increased, suggesting that captopril, together with a release of active renin, may induce an in vivo activation of inactive renin. No correlations were found between blood pressure changes and both pretreatment and captopril-induced variations of active, inactive and trypsin-activated renin or the active/inactive ratio. However, the percent decrease in mean arterial pressure was significantly related to the increase in the active/inactive renin ratio in a group of patients whose blood pressure was brought to normal (r = -0.78; p less than 0.001). This finding suggests the possibility that vasodilating substances, in addition to inhibiting angiotensin II formation, might play some role both in exerting a full effect of captopril on blood pressure and in triggering the in vivo mechanisms of inactive renin activation.

In-vivo activation of circulating inactive renin by the ischemic kidney in man.

The role of the kidney as a possible source or as activator of inactive renin was studied in 22 patients with Essential Hypertension (EH) and in 20 patients with Unilateral Renal Artery Stenosis (RAS). Active and inactive renin (trypsin activation) were measured in blood samples taken simultaneously from both renal veins and from a peripheral artery during acute diuretic stimulation induced by furosemide 40 mg i.v. In EH pts active and trypsin-activated renin were significantly higher in both renal veins than in arterial blood (P less than 0.001 and P less than 0.02 respectively) whereas no difference was seen as far as inactive renin is concerned. In unilateral RAS trypsin-activated and active renin from the ischemic kidney were significantly higher (P less than 0.01 and P less than 0.005 respectively) while inactive renin was significantly lower (P less than 0.005) than in arterial blood. No significant difference was seen between arterial and renal venous blood from the contralateral kidney as far as active and inactive renin are concerned. When comparing the V-A differences for active renin to the corresponding V-A differences for inactive renin from the ischemic kidney a significant negative correlation appeared (r = -0.49 p less than 0.05) whereas no correlation was found from the contralateral kidney (r = -0.26 n.s.). These data demonstrate that the ischemic kidney, in addition to its ability to release active renin, can also activate circulating inactive renin.

Plasma active and inactive renin and urinary kallikrein in normal subjects in response to hydrochlorothiazide, spironolactone or aldosterone administration.

The aim of this study has been to see whether acute variations in the proportions of circulating active and inactive renin in normal subjects were related to concurrent changes in the excretion of urinary kallikrein. Hydrochlorothiazide (50 mg/day) was given to 6 normal volunteers for 6 days; another group of 6 normal subjects received spironolactone (300 mg/day) for 6 days whereas synthetic aldosterone (0.5 mg/day) was administered i.m. for three days to 3 normal subjects. Both diuretics induced a sharp rise in active and total renin and a significant transient decrease in inactive renin so that the active: total renin proportion significantly increased. Urinary kallikrein excretion did not significantly change in either group. Parenteral administration of aldosterone induced a striking fall in all renin components without changing the proportions of active and inactive renin whereas urinary kallikrein excretion increased. These results indicate that changes in active: total renin proportions can occur without parallel variations in urinary kallikrein excretion. The latter cannot be used, therefore, as a reliable index of the possible role of renal kallikrein as activator in-vivo of inactive renin in man.

[Role of renin profile and age in the choice of the therapeutic approach of arterial hypertension (author's transl)]. / Ruolo del profilo reninico e dell'età nella scelta dell'approccio terapeutico dell'ipertensione arteriosa.

A group of 116 patients with grade I-II (W.H.O.) essential hypertension was studied. A diuretic treatment was instituted as a first step of therapy in 50 patients while the remaining 66 were firstly treated with beta-blockers. After 6 weeks of treatment the drugs were combined in those patients who did not achieve blood pressure control; this combination therapy was again maintained for 6 weeks and, if necessary, a vasodilating agent was added thereafter. The results show that with diuretic treatment alone diastolic blood pressure was brought to normal values (less than 95 mmHg) in 3/4 of our low renin patients, in 2/3 of normal renin and in 1/3 of high renin hypertensives. On the contrary among the group of patients treated with a beta-blocker alone more than half of the high and normal renin patients were controlled whereas this goal was achieved in only 1/4 of the low renin patients. Similar behaviour was observed subdividing the subjects in young (less than 35 yrs), middle-aged (36-49 yrs) and older (greater than 50 yrs) patients. In conclusion our data indicate that age must be taken into account in classifying hypertensive patients in renin subgroups. In addition if a renin-sodium profile is available, it can be useful in choosing between diuretics or beta-blocker as a first step treatment. Alternatively, younger patients are more likely to have better hypotensive responses with beta-blockers whereas in older patients antihypertensive treatment should preferentially be started with diuretics alone.