Piergiorgio Zuccaro

Effect of the Italian Smoking Ban on Population Rates of Acute Coronary Events

Background— Several countries in the world have not yet prohibited smoking in public places. Few studies have been conducted on the effects of smoking bans on cardiac health. We evaluated changes in the frequency of acute coronary events in Rome, Italy, after the introduction of legislation that banned smoking in all indoor public places in January 2005. Methods and Results— We analyzed acute coronary events (out-of-hospital deaths and hospital admissions) between 2000 and 2005 in city residents 35 to 84 years of age. We computed annual standardized rates and estimated rate ratios by comparing the data from prelegislation (2000–2004) and postlegislation (2005) periods. We took into account several time-related potential confounders, including particulate matter (PM10) air pollution, temperature, influenza epidemics, time trends, and total hospitalization rates. The reduction in acute coronary events was statistically significant in 35- to 64-year-olds (11.2%, 95% CI 6.9% to 15.3%) and in 65- to 74-year-olds (7.9%, 95% CI 3.4% to 12.2%) after the smoking ban. No evidence was found of an effect among the very elderly. The reduction tended to be greater in men and among lower socioeconomic groups. Conclusions— We found a statistically significant reduction in acute coronary events in the adult population after the smoking ban. The size of the effect was consistent with the pollution reduction observed in indoor public places and with the known health effects of passive smoking. The results affirm that public interventions that prohibit smoking can have enormous public health implications.

The Effect of Zinc and Vitamin A Supplementation on Immune Response in an Older Population

OBJECTIVE: To determine if either supplemental vitamin A, zinc, or both increases cell‐mediated immune response in an older population.

Exposure to fine and ultrafine particles from secondhand smoke in public places before and after the smoking ban, Italy 2005

Background: A smoking ban in all indoor public places was enforced in Italy on 10 January 2005. Methods: We compared indoor air quality before and after the smoking ban by monitoring the indoor concentrations of fine (<2.5 μm diameter, PM2.5) and ultrafine particulate matter (<0.1 μm diameter, UFP). PM2.5 and ultrafine particles were measured in 40 public places (14 bars, six fast food restaurants, eight restaurants, six game rooms, six pubs) in Rome, before and after the introduction of the law banning smoking (after 3 and 12 months). Measurements were taken using real time particle monitors (DustTRAK Mod. 8520 TSI; Ultra-fine Particles Counter-TRAK Model 8525 TSI). The PM2.5 data were scaled using a correction equation derived from a comparison with the reference method (gravimetric measurement). The study was completed by measuring urinary cotinine, and pre-law and post-law enforcement among non-smoking employees at these establishments Results: In the post-law period, PM2.5 decreased significantly from a mean concentration of 119.3 μg/m3 to 38.2 μg/m3 after 3 months (p<0.005), and then to 43.3 μg/m3 a year later (p<0.01). The UFP concentrations also decreased significantly from 76 956 particles/cm3 to 38 079 particles/cm3 (p<0.0001) and then to 51 692 particles/cm3 (p<0.01). Similarly, the concentration of urinary cotinine among non-smoking workers decreased from 17.8 ng/ml to 5.5 ng/ml (p<0.0001) and then to 3.7 ng/ml (p<0.0001). Conclusion: The application of the smoking ban led to a considerable reduction in the exposure to indoor fine and ultrafine particles in hospitality venues, confirmed by a contemporaneous reduction of urinary cotinine.

Drugs in nails: Physiology, pharmacokinetics and forensic toxicology

In recent years, drug analysis in keratinised matrices, such as hair and nails, has received considerable attention because of several advantages over drug testing methodologies employing body fluids, such as urine or serum. For example, keratinic matrices, such as finger- and toenails, can accumulate drugs during long term exposure. Drugs are incorporated into nails by a double mechanism: (i) deposition into the root of the growing nail via the blood flow in the nail matrix; and (ii) incorporation via the nail bed during growth from the lunula to the beginning of the free margin. Together, these account for a wide retrospective window of drug detection.Nails can provide a good forensic matrix for the detection of drugs of abuse. Indeed, the international literature has reported the use of nail analysis in postmortem detection of drugs of abuse, drug testing in the workplace and drug screening to detect prenatal exposure, even though further studies are needed for correct interpretation of the data obtained.Another application of drug analysis in nails consists of the possibility of detecting the presence of an antimycotic at the site of action during antifungal therapy for patients with onychomycosis. When available, this evidence has permitted drug treatment of a shorter duration and reduced toxicity However, so far the potential of drug monitoring in nails still lacks harmonisation and validation of analytical methodologies and a better comprehension of the possible correlation between drug concentrations in the matrix and period of exposure.

Clinical Pharmacokinetics of Amfetamine and Related Substances Monitoring in Conventional and Non-Conventional Matrices

Consumption of amfetamine-type stimulants, including classical amfetamines and ‘designer drugs’, has been recognised as one of the most significant trends in drug abuse at the end of the past century and at the beginning of the current one. The first cause is the increasing consumption amongst youth of methylenedioxy- and methoxy-substituted amfetamines, of which the pharmacology in humans is currently under investigation. Secondly, the abuse of more classical amfetamines, such as amfetamine itself and metamfetamine, continues to be highly prevalent in some geographical regions.Amfetamines are powerful psychostimulants, producing increased alertness, wakefulness, insomnia, energy and self-confidence in association with decreased fatigue and appetite as well as enhanced mood, well-being and euphoria. From a clinical pharmacokinetic perspective, amfetamine-type stimulants are rather homogeneous. Their oral bioavailability is good, with a high distribution volume (4 L/kg) and low binding to plasma proteins (less than 20%). The elimination half-life is 6–12 hours. Both hepatic and renal clearance contribute to their elimination from the body. Hepatic metabolism is extensive in most cases, but a significant percentage of the drug always remains unaltered.Amfetamine and related compounds are weak bases, with a pKa around 9.9, and a relatively low molecular weight. These characteristics allow amfetamine-type stimulants to diffuse easily across cell membranes and lipid layers and to those tissues or biological substrates with a more acidic pH than blood, facilitating their detection in alternative matrices at relatively high concentrations. In most cases, the concentrations found are higher than expected from the Henderson-Hasselbach equation. Drug monitoring in non-conventional biological matrices (e.g. saliva, hair, nails, sweat) has recently gained much attention because of its possible applications in clinical and forensic toxicology. An individual’s past history of medication, compliance or drug abuse can be obtained from testing of hair and nails, whereas data on current status of drug use can be provided by analysis of sweat and saliva.Because of the physicochemical properties of amfetamine-type stimulants, this group of drugs is one of the most suitable for drug testing in non-conventional matrices.

Pharmacokinetics and cytokine production in heroin and morphine-treated mice

The parallelism between serum levels of heroin and morphine (M) metabolites and the production of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), and interferon-gamma (IFN-gamma) from murine splenocyte cultures following s.c. injection with 20 mg/kg heroin or M in C57/BL mice is described. The pharmacokinetic profiles of M and inactive morphine-3-glucuronide (M3G) in morphine-treated mice nearly overlapped those in heroin-treated mice, with the only difference being the presence of 6-monoacetylmorphine (AM) in profiles of the latter group. Heroin and M significantly increased production of IL-1beta, IL-2, TNF-alpha and IFN-gamma at 3, 20 and 40 min from treatment, peaking at 20 min, though the effect was very brief. At 24 h production was greatly inhibited, and this depressive effect lasted longer than the stimulatory effect. At 48 h only a partial recovery was observed. Heroin and M also had a highly stimulatory effect on the release of anti-inflammatory cytokines such as TGF-beta1 and IL-10, though this effect was observed after 120 min, peaking at 24 h and then somewhat decreasing at 48 h. This study demonstrates that the more rapid and pronounced immune response to heroin treatment was due to the presence of AM. Both heroin and M produced a biphasic effect on cytokine production: the central opioid or non-opioid receptors are involved in exogenous opiod-induced stimulatory effects, whereas peripheral opioid or non-opioid receptors are involved in depressive effects. Deficient or excess expression of these key mediators may predispose the host to aberrant defence mechanisms.

Nicotine, cotinine, and trans-3-hydroxycotinine levels in seminal plasma of smokers: Effects on sperm parameters

Sperm samples from 44 cigarette smokers and 50 nonsmokers attending an infertility clinic were examined by high-performance liquid chromatography (HPLC) assay and HPLC-mass spectrometry for the presence of nicotine (NIC), cotinine (COT), and trans-3‘-hydroxycotinine (THOC) in seminal plasma. Smokers were found to have levels of COT and THOC in seminal plasma that were similar to those found in serum. The level of NIC was significantly increased in seminal plasma compared to serum. Total motility of spermatozoa was significantly and negatively correlated to COT and THOC levels in seminal plasma. Forward motility of spermatozoa was correlated only with cotinine semen levels. On the basis of these results, we suggest that the presence of tobacco smoke constituents in seminal plasma could provide a warning of the adverse effects of cigarette smoke on the physiology of reproduction.

Drug monitoring in nonconventional biological fluids and matrices

SummaryDetermination of the concentration of drugs and metabolites in biological fluids or matrices other than blood or urine (most commonly used in laboratory testing) may be of interest in certain areas of drug concentration monitoring.Saliva is the only fluid which can be used successfully as a substitute for blood in therapeutic drug monitoring, while an individual’s past history of medication, compliance and drug abuse, can be obtained from drug analysis of the hair or nails. Drug concentrations in the bile and faeces can account for excretion of drugs and metabolites other than by the renal route. Furthermore, it is important that certain matrices (tears, nails, cerebrospinal fluid, bronchial secretions, peritoneal fluid and interstitial fluid) are analysed, as these may reveal the presence of a drug at the site of action; others (fetal blood, amniotic fluid and breast milk) are useful for determining fetal and perinatal exposure to drugs. Finally, drug monitoring in fluids such as cervical mucus and seminal fluid can be associated with morpho-physiological modifications and genotoxic effects.Drug concentration measurement in nonconventional matrices and fluids, although sometimes expensive and difficult to carry out, should therefore be considered for inclusion in studies of the pharmacokinetics and pharmacodynamics of new drugs.

Morphine and methadone impact on human phagocytic physiology

Human subjects submitted to treatment with morphine show a severe depression of phagocytosis, killing properties and superoxide production both of their polymorphonuclear leukocytes and monocytes. Polymorphonuclear leukocyte adherence, chemotaxis, random migration, myeloperoxidase content, lysozyme content and lymphocyte Rosette E formation were poorly influenced. Methadone-treated subjects show a similar effect at phagocytic level but far less evident. These results confirm those previously found in animals and reinforce the evidence of a depressive role of morphine on phagocytic physiology.

Overweight and obesity in Italian adults 2004, and an overview of trends since 1983

Objective:Overweight has been increasing in several developed countries over the last few decades. No update information on the issue is available for Italy.Design and setting:We conducted a computer assisted personal in-house interview survey in March–April 2004, on a sample of 2932 Italian individuals (1407 men and 1525 women) aged 18 years or over, representative of the general adult Italian population. Information on weight and height was self-reported.Results:Overall, 3.4% of the Italian adult population were underweight (<18.5 kg/m2, 0.9% of men and 5.8% of women), 31.3% were overweight (25.0–29.9 kg/m2, 38.4% of men, 24.7% of women), and 8.2% were obese (⩾30.0 kg/m2, 7.4% of men and 8.9% of women). Overweight or obesity was reported by 14.2% of subjects aged 18–24 years (20.6% of men and 7.6% of women). The highest proportions of overweight and obese subjects were in the 45–64 year age group for men (51.4% overweight, 10.0% obese) and in the ⩾65 year age group for women (38.8% overweight, 13.8% obese). Age- and sex-standardised prevalence of overweight or obesity was 36.0% for more educated subjects, and 54.0% for less educated ones. It was 32.3% in northern, 44.3% in central and 47.0% in southern Italy. Overweight increased from 1983 to the early 1990s, and levelled off thereafter. Prevalence of obesity remained around 8–9% across the last 20 years.Conclusions:Trends of overweight and obesity in Italy are more favourable than in several developed countries. Still, approximately 15 million of Italian adults are overweight and 4 million obese.