Use and perceived benefits of complementary therapies by cancer patients receiving conventional treatment in Italy.

CONTEXT: In Italy, data regarding the use of complementary therapies (CTs) among patients with cancer are sparse and discordant. OBJECTIVES: The present study aimed to investigate the demographic and psychological characteristics of Italian cancer patients who use CTs and the perceived benefit of users. METHODS: Eight hundred three patients from six Italian oncology departments were interviewed about CT use and completed two questionnaires to explore psychological distress and the resilience trait called sense of coherence (SOC). Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. RESULTS: At the time of measurement, 37.9% of patients were using one or more types of CTs. The most commonly used CTs were diets and dietary supplements (27.5%), herbs (10.8%), homeopathy (6.4%), and mind-body therapies (5.5%). The Italian context is characterized by a high percentage of patients who informed their physicians about CT use (66.3%) and who experienced benefits (89.6%); 75.2% of the patients had used CTs in the past. Multivariate analysis revealed that young, female patients, who previously used complementary and alternative medicine in the past, appear more likely to use at least one type of CT in the present. Predictors of the use of CTs varied according to the type of CT. Among psychological factors, SOC was positively associated with both past and present CT use. CONCLUSION: Overall prevalence of CTs among Italian cancer patients is high and is in accordance with the European average. In addition to clinical and sociodemographic factors, the resilience trait SOC also was associated with CT use.

Use, Attitudes and Knowledge of Complementary and Alternative Drugs (CADs) Among Pregnant Women: a Preliminary Survey in Tuscany.

To explore pregnant women's use, attitudes, knowledge and beliefs of complementary and alternative drugs (CADs) defined as products manufactured from herbs or with a natural origin. A preliminary survey was conducted among 172 pregnant women in their third trimester of pregnancy, consecutively recruited in two obstetrical settings; 15 women were randomly selected to compute a test-to-retest analysis. Response rate was 87.2%. Test-to-retest analysis showed a questionnaire's reproducibility exceeding a K-value of 0.7 for all items. Mean age was 32.4 ± 0.4 years; most women were nulliparae (62.7%). The majority of subjects (68%) declared to have used one or more CADs during their lifetime; 48% of pregnant women reported taking at least one CAD previously and during the current pregnancy. Women's habitual use of CADs meant they were at higher risk of taking CADs also during pregnancy (adjusted odds ratio = 10.8; 95% confidence interval: 4.7-25.0). Moreover, 59.1% of the subjects were unable to correctly identify the type of CADs they were using. The majority of women resorted to gynecologists as the primary information source for CADs during pregnancy, while they mainly referred to herbalists when not pregnant. Habitual use of CADs seems to be a strong predictor for their ingestion also during pregnancy; in addition most subjects were unable to correctly identify the products they were taking. In the light of the scanty data concerning the safety of CADs during pregnancy, these preliminary results confirm the need to investigate thoroughly the situation of pregnant women and CADs consumption.

Safety aspects of iodinated contrast media related to their physicochemical properties: a pharmacoepidemiology study in two Tuscany hospitals.

BACKGROUND: More than 380,000 angiographic procedures are performed every year in Italian hospitals, with an increase rate of 8% per year. Although contrast media (CM) are considered relatively safe, adverse drug reactions (ADRs) remain an important issue. OBJECTIVES: The objective of this study was to quantify the incidence of immediate and delayed nonrenal ADRs to iodinated CM in an Italian cohort and to evaluate whether their different physicochemical properties are able to affect the incidence of immediate or delayed ADRs. METHODS: A prospective intensive monitoring study was conducted on a cohort of patients undergoing radiodiagnostic procedures with iodinated CM enrolled in two hospitals in Tuscany, Italy. To evaluate both immediate (within 1 h after CM administration) and delayed (>1 h to 1 week after CM administration) ADRs to CM, two questionnaires were administered. Adverse events (AEs) were analyzed to check the causality assessment between CM and ADR. If more than one symptom occurred in the same patient, they were treated as a single event. RESULTS: One thousand five hundred and fourteen subjects who were exposed to iodinated CM completed the questionnaires. Mean age [standard deviation (SD)] was 65.4 (13.3) years, and 57.9% were male patients. A total of 178 [11.8%; 95% confidence interval (CI) 10.1-13.4] ADRs were reported. Thirty-four (2.2%; 1.5-3.1) and 144 (9.5%; 8.0-11.1) developed immediate and delayed ADRs, respectively. Both types of ADRs were experienced by six subjects (0.4%; 0.1-0.8). One hundred and seventy-six cases (98.8%; 96.0-99.8) were classified as possible and two (1.1%; 0.1-3.9) as probable ADRs. Monomeric low-osmolal (iopromide, iomeprol, iobitridol) and dimeric iso-osmolal (iodixanol) groups mainly reported delayed allergy-like ADRs of mild severity. Only one immediate reaction was severe. Multivariate analysis confirmed a higher risk of immediate reactions occurring for monomeric CM (OR 4.3; 95% CI 1.2-15.7), whereas the risk of delayed ADRs was significantly higher for the dimeric group (OR 1.8; 1.1-2.5). CONCLUSIONS: Monomeric CM were more frequently involved in immediate ADRs, whereas dimeric CM were involved in delayed reactions. Although severe life-threatening ADRs to CM were confirmed to be rare, due to the large use of these drugs, they still retain clinical and epidemiological significance.

Methylamine: a new endogenous modulator of neuron firing?

Increasing evidence suggests that not only ammonia, but also its alkyl-derivatives, including methylamine, may modulate neuron firing. Methylamine occurs endogenously from amine catabolism and its tissue levels increase in some pathological conditions, including diabetes. Interestingly, methylamine and ammonia levels are reciprocally controlled by a semicarbazide-sensitive amine oxidase activity that deaminates methylamine to formaldehyde with the production of ammonia and hydrogen peroxide. As already described for ammonia, methylamine also targets the voltage-operated neuronal potassium channels, probably inducing release of neurotransmitter(s). From this interaction it has been observed that methylamine is 1) hypophagic in mice without producing amphetamine-like effects and 2) a stimulator of nitric oxide release from rat hypothalamus. Methylamine hypophagia is also maintained in genetically obese and diabetic mice and is increased when these animals are pre-treated with -amino guanidine, an inhibitor of methylamine oxidative deamination. The effect of -amino guanidine suggests a potential beneficial effect of this drug, and other such inhibitors, in controlling food intake in animals with disturbed eating behavior. Moreover, the activity of methylamine as an inducer of NO release suggests a role for the amine and for the enzymatic activity that degrades it in neurodegenerative diseases.

n-3 polyunsaturated fatty acids supplementation decreases asymmetric dimethyl arginine and arachidonate accumulation in aging spontaneously hypertensive rats.

BACKGROUND: Plasma accumulation of asymmetric dimethyl arginine (ADMA) is considered as a risk factor for endothelial dysfunction and a strong predictor for coronary heart diseases. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) increasing plasma levels have been positively associated with reduced cardiovascular mortality with a mechanism( s) yet unclear. We hypothesised that ADMA reduction might be a part of EPA and DHA beneficial effects on the cardiovascular system. AIM: To verify this hypothesis we measured ADMA plasma levels in aged spontaneously hypertensive rats (SHR) supplemented for 8 weeks with EPA and DHA. METHODS: 16-month-old SHR were supplemented with EPA and DHA (EPA-DHA) or with olive oil (1 g/kg/day; OLIVE). At the end of the treatments, the plasma of each animal was analysed for 1) the total fatty acid composition, by gas-cromatography, 2) ADMA levels, by high pressure liquid chromatography, 3) nitrite and homocysteine concentration by chemiluminescence and by polarisation immunoassay respectively. Moreover, the activity of dimethyl arginine dimethyl amino hydrolase, the main enzyme involved in ADMA metabolism, was measured spectrophotometrically in the kidney from each rat. RESULTS: Animals supplemented with EPA and DHA showed: 1) lower ADMA and arachidonate plasma levels (587.4 +/- 113.7 nM and 0.49 +/- 0.11 mM respectively) than the values found in OLIVE rats (1365 +/- 399 nM and 1.07 +/- 0.07 mM respectively) 2) higher nitrite content (0.73 +/- 0.05 microM) than OLIVE (0.23 +/- 0.08 microM). CONCLUSIONS: EPA and DHA supplementation reduced ADMA accumulation in SHR in parallel with a decrease of arachidonate availability. This finding suggests that the control of the inflammatory ground of endothelium might play an important role in EPA and DHA effect on this novel and highly predictive cardiovascular risk factor.

Pancreatitis induced by pegylated interferon alfa-2b in a patient affected by chronic hepatitis C.

A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and fainting. A blood analysis revealed high levels of serum amylase and lipase, confirming a diagnosis of acute pancreatitis. The history showed that the patient had self-administered a single dose of pegylated interferon alfa-2b and ribavirin daily for 7 days for chronic hepatitis C. The medications were stopped and his condition gradually improved. In agreement with the literature and the Naranjo algorythm result, pegylated interferon alfa-2b is associated with acute pancreatitis. Identification of a few signs and symptoms is the first 'signal' in preventing a serious drug-induced adverse event.

Restoration of cardiomyocyte functional properties by angiotensin II receptor blockade in diabetic rats.

Recent evidence suggests that blockade of the renin-angiotensin system ameliorates diabetes-induced cardiac dysfunction, but the mechanisms involved in this process remain elusive. We investigated the effect of treatment with an angiotensin II receptor blocker, losartan, on the metabolic and electrophysiological properties of cardiomyocytes isolated from streptozotocin-induced diabetic (STZ) rats. Glucose uptake and electrophysiological properties were measured in ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 20 mg x kg(-1) x day(-1) losartan for 8 weeks. Insulin and beta-adrenergic stimulation failed to increase the glucose uptake rate in STZ cardiomyocytes, whereas the alpha-adrenergic effect persisted. Concurrently, a typical prolongation of action potential duration (APD) and a decrease of transient outward current (I(to)) were recorded in patch-clamped STZ myocytes. Treatment with losartan did not affect body weight or glycemia of diabetic or control animals. However, in losartan-treated STZ-induced diabetic rats, beta-adrenergic-mediated enhancement of glucose uptake was completely recovered. APD and I(to) were similar to those measured in losartan-treated control rats. A significant (P < 0.0001) correlation between metabolic and electrophysiological parameters was found in control, diabetic, and losartan-treated diabetic rats. Thus, angiotensin receptor blockade protects the heart from the development of cellular alterations typically associated with diabetes. These data suggest that angiotensin receptor blockers may represent a new therapeutic strategy for diabetic cardiomyopathy.

Antisense knockdown of the Shaker-like Kv1.1 gene abolishes the central stimulatory effects of amphetamines in mice and rats.

Amphetamine (AMPH) is an indirect sympathomimetic compound classified as a substrate-type releaser that distinguishes it from other stimulants that act as uptake 1 blockers, such as cocaine (COC). In mammals, AMPH elicits central stimulation, hypermotility, anorexia, analgesia and analeptic activity, mainly through the increase of extracellular brain dopamine (DA). The inversion of vesicular transporters and/or intravesicular alkalinization is assumed to have a role in AMPH-induced exocytosis. However, the action mechanism of this compound has not yet been completely clarified. Recent evidence on the action of AMPHs indicates potassium channel-blocking properties in peripheral tissues. We investigated the possible involvement of a Shaker-like Kv1.1 channel subtype in the central effects of AMPH, using an antisense oligodeoxyribonucleotide (aODN) that specifically and reversibly inhibits the expression of these channels in the brain. The effect of aODN pretreatments was studied by evaluating the modification of behavioral effects induced in mice through the intracerebroventricular administration of AMPH, COC, or other compounds. The aODN in mice almost completely blocked the stimulatory effects of AMPH and other releasers but was ineffective in reducing the central activity of COC. In aODN-pretreated rats a strong reduction of the AMPH, but not of the COC-stimulated DA efflux from nucleus accumbens was observed. Our results suggest that the stimulant effects of AMPH and chemically related compounds, but not COC, require the presence of functionally active Kv1.1 channels in the brain.

The direct stimulation of Gi proteins by neuropeptide Y (NPY) in the rat left ventricle.

Neuropeptide Y (NPY) is a neuropeptide with high distribution in the cardiovascular system of mammals, where it modulates heart and vessel contractility. In the rat heart, the presence of at least three different NPY receptor subtypes has been hypothesised. Notwithstanding this, receptor activation might not be the only mechanism responsible for the complex cardiac effects of the peptide. In this study, we investigated the effect of NPY on the GTPase activity of G-proteins in the rat left ventricle as a possible alternative mechanism of action for the peptide in the rat heart. Our results show that NPY, but also the neuropeptide fragment (18-36) (NPY (18-36)), stimulated the basal, spontaneous GTPase activity of ventricle membranes only when it was measured under the condition of an absence of Mg2+. This stimulation was resistant to BIBP3226 a non-peptidergic antagonist at Y1 receptors, but it was significantly reduced in membranes treated with selective antibodies against the Gialpha subunits. NPYs effect was concentration-dependent with a maximum of activity at 10nM. At this concentration, NPY (and NPY 18-36) was able to inhibit forskolin (FSK)-induced cyclic adenosine-5'-monophosphate (cAMP) elevation in rat left ventricle slices. Our results assess that NPY in the rat heart is able to activate the GTPase activity of Gi proteins, in a receptor-independent way.