Risk factors for deliberate self-poisoning among children and adolescents in The Netherlands.

INTRODUCTION: In the past decade, the number of deliberate self-poisonings involving young people has increased strongly worldwide. This study aimed to gain insight into risk factors associated with deliberate self-poisonings among children and adolescents reported to the Dutch Poisons Information Center. METHODS: A study was performed between 1 February 2022 and 31 January 2023 involving those aged 8-17 years of age with deliberate self-poisoning. Data were collected on patient characteristics (age, gender, body mass index and living situation) and exposure characteristics (type of toxicant, way of acquiring toxicant and day of exposure). RESULTS: The Dutch Poisons Information Center was consulted about 1,424 deliberate self-poisonings among children and adolescents (10-17 years old). A high percentage of patients were female (85 percent), had a body mass index classified as overweight/obese (27 percent) and lived in a mental healthcare facility (13 percent). Patients mainly exposed themselves to pharmaceuticals, especially over-the-counter medications such as paracetamol (46 percent) and ibuprofen (15 percent). Young people living with parents/caregivers had higher odds of ingesting prescription pharmaceuticals or over-the-counter medication, while those living in a mental healthcare facility were more likely to ingest household products, personal care products or foreign bodies (predominantly batteries). DISCUSSION: This study sheds light on the pervasive issue of deliberate self-poisoning among children and adolescents, advocating for poisoning prevention strategies and promoting mental health of youth. Limitations include reliance on self-reported data from patients and the absence of clinical outcome data. CONCLUSIONS: Female gender, a high body mass index and living in a mental healthcare facility are associated with in increased risk of deliberate self-poisonings in children and adolescents (10-17 years old). Prevention of deliberate self-poisonings among youth could focus on restricting access to medication and other potentially hazardous non-pharmaceuticals, such as household products and batteries, as well as limiting the sales of over-the-counter medication, especially paracetamol, to this young population.

Preventing occupational chemical eye injuries: important lessons from poison information centres.

BACKGROUND: Occupational exposure to hazardous substances is a major public health problem. In the workplace, eye exposures are common and can be a major cause of morbidity and disability. This commentary discusses the role of poison information centres in providing valuable information on the circumstances and causes of these incidents. OCCUPATIONAL HEALTH SURVEILLANCE: As many eye exposures are easily preventable, there is a need to establish better safety practices in the workplace. Currently, both governments and labour organizations primarily employ injury statistics for the purpose of occupational health surveillance. Identifying risk factors associated with acute exposures in the workplace requires a comprehensive approach using a variety of information resources. Using information from poison information centres can provide invaluable insight into the specifics of the exposure, including the route(s) of exposure, the substances involved and the cause of the exposure. CIRCUMSTANCES OF OCCUPATIONAL EYE EXPOSURES: Exposure to hazardous substances can occur at various time points during work. A prospective study performed by the Dutch Poisons Information Centre showed that cleaning is a high-risk activity for occupational eye exposure. Patients were often exposed to chemical mixtures that frequently contained alkalis or acids. CHEMICAL EYE INJURIES: Symptoms following eye contact with chemicals can vary greatly depending on factors such as the type and concentration of the substance(s) involved, the duration of exposure and the time and duration of irrigation (first-aid measure). Eye contact will usually cause irritation, but in more severe cases, chemical burns will result. Recent studies demonstrate that occupational eye exposures often result in only relatively mild symptoms, such as pain, redness, lacrimation or temporary loss of vision. More severe symptoms, such as corneal abrasion, were reported rarely, which may be explained by prompt eye irrigation. ROOT CAUSES OF OCCUPATIONAL EYE EXPOSURES: To control risks to workers, a hierarchy of prevention and control measures has been established, which employers must take. If elimination or substitution of the dangerous substance is not possible, the exposure can be prevented or reduced by taking organizational (e.g., providing work instructions), technical (e.g., ventilation) and personal (e.g., wearing personal protective equipment) measures. The study performed by the Dutch Poisons Information Centre showed that organizational factors (such as lack of work instructions) and personal factors (such as time pressure and fatigue, and not (adequately) using personal protective equipment), were the main causes of occupational eye exposure. CONCLUSIONS: Poison information centres provide valuable information that can be used to develop prevention strategies to reduce the number of acute occupational exposures in the future. A multidisciplinary approach is essential to ensure that these preventive measures are actually applied in practice. Therefore, all organizations involved (including governments, labour organizations, medical professionals, occupational physicians, occupational hygienists, safety experts and poison information centres) must work closely together.

Causal factors of work-related chemical eye injuries reported to the Dutch Poisons Information Center.

This study investigated the circumstances of chemical occupational eye exposures reported to the Dutch Poisons Information Center. During a 1-year prospective study, data were collected through a telephone survey of 132 victims of acute occupational eye exposure. Victims were often exposed to industrial products (35%) or cleaning products (27%). Most patients developed no or mild symptoms. Organizational factors (such as lack of work instructions (52%)), and personal factors (such as time pressure and fatigue (50%), and not adequately using personal protective equipment (PPE, 14%), were the main causes of occupational eye exposures. Exposure often occurred during cleaning activities (34%) and personal factors were reported more often during cleaning (67%) than during other work activities (41%). Data from Poison Control Centers are a valuable source of information, enabling the identification of risk factors for chemical occupational eye exposure. This study shows that personal factors like time pressure and fatigue play a significant role, although personal factors may be related to organizational issues such as poor communication. Therefore, risk mitigation strategies should focus on technical, organizational, and personal factors. The need to follow work instructions and proper use of PPE should also have a prominent place in the education and training of workers.

Significant Increase in Deliberate Self-Poisonings Among Adolescents During the Second Year of the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic has been associated with a decline in mental health of adolescents. The aim of this study was to analyze the rate of deliberate self-poisonings (DSPs) among adolescents reported to the Dutch Poisons Information Center before and during the COVID-19 pandemic. METHODS: A retrospective study from 2016 until 2021 was performed to characterize DSPs among adolescents, and to analyze trends in the number of DSPs. All DSPs among adolescents with the age of 13 up to and including 17 years were included. DSP characteristics included: age, gender, bodyweight, used substance, dose, and treatment advice. Trends in the number of DSPs were analyzed using time series decomposition and Seasonal Autoregressive Integrated Moving Average models. RESULTS: Six thousand nine hundred fifteen DSPs in adolescents were recorded from January first 2016 until December 31st 2021. Females were involved in 84% of adolescent DSPs. A strong increase in the number of DSPs was observed in 2021 (45% increase compared to 2020), which deviated from the predicted trend based on previous years. This increase was most prominent in 13-, 14-, and 15-year-old female adolescents. Commonly involved drugs were paracetamol, ibuprofen, methylphenidate, fluoxetine, and quetiapine. The contribution of paracetamol rose from 33% in 2019 to 40% in 2021. DISCUSSION: The strong increase in the number of DSPs during the second year of the COVID-19 pandemic suggests that long-term containment measures such as quarantines, lockdowns, and school closures may enhance self-harm behavior among adolescents, especially among younger females (13-15 years of age), with a preference for paracetamol as DSP substance.

Acute occupational exposures reported to the Dutch Poisons Information Center: a prospective study on the root causes of incidents at the workplace.

BACKGROUND: Hazardous substances at the workplace can cause a wide variety of occupational incidents. This study aimed to investigate the nature and circumstances of acute occupational intoxications reported to the Dutch Poisons Information Center. METHODS: During a one-year prospective study, data on the circumstances and causes of the incident, the exposure(s) and clinical course, were collected by a telephone survey with victims of an acute occupational intoxication. RESULTS: We interviewed 310 patients. Most incidents occurred in industry (25%), building and installation industry (14%) and agriculture (10%). Patients were often exposed via multiple routes. Inhalation was the most common route of exposure (62%), followed by ocular (40%) and dermal contact (33%). Acids and alkalis were often involved. Exposure often occurred during cleaning activities (33%). The main root causes of these accidents were: technical factors such as damaged packaging (24%) and defective apparatus (10%), organizational factors such as lack of work instructions (44%) and poor communication or planning (31%), and personal factors such as disregarding work instructions (13%), not (adequately) using personal protective equipment (12%) and personal circumstances (50%) such as inaccuracy, time pressure or fatigue. The majority of the patients only reported mild health effects and recovered quickly (77% within 1 week). CONCLUSIONS: Poison Center data on occupational exposures provide an additional source of knowledge and an important basis for poisoning prevention strategies related to hazardous substances at the workplace. These data are useful in deciding which risk mitigation measures are most needed in preventing future workplace injuries.

Poisoning in older adults: characterization of exposures reported to the Dutch Poisons Information Center.

Introduction: The annual number of patients > 65 years old about whom the Dutch Poisons Information Center (DPIC) was consulted has more than doubled in the last decade. We aimed to gain insight in the type and circumstances of exposures reported to the DPIC involving older patients, in order to help prevent future poisonings. Methods: Enquiries to the DPIC involving patients > 65 years old were prospectively included from January 2019 to June 2019. Data were collected on patient characteristics (e.g., age, gender, and living situation) and exposure characteristics (e.g., type and exposure scenario). Results: In the first half of 2019, the DPIC was consulted about 1051 patients > 65 years old. The median age of the patients was 77 years old (range: 66-104 years) and women were over-represented (61%). A total of 1650 different substances were reported, 1213 pharmaceutical exposures (74%) and 437 non-pharmaceutical exposures (26%), mostly household products (n = 162). Most pharmaceutical exposures involved cardiovascular agents (n = 367, 30%), central and peripheral nervous system agents (n = 354, 29%), and analgesics (n = 152, 13%). In 71% of the patients exposed to pharmaceuticals, the drugs were taken unintentionally (n = 471), frequently caused by medication errors made by the patients themselves (n = 357, 76%). Most common scenarios included inadvertently taken/given a double (n = 140, 30%) or more than double (n = 94, 20%) dose or the wrong medication (n = 124, 26%). The most common scenario for unintentional exposure to non-pharmaceuticals was "mistook product for food/drink" (n = 122, 37%). Conclusions: The majority of intoxications in older adults are accidental and often involve medication errors. Unintentional poisoning is often preventable. If patients are cognitively impaired, potentially harmful substances should be kept out of their reach and medication should only be administered under direct supervision. Clear labelling, simplified drug regimens and the use of automatic medication dispensers could reduce the risk of medication errors in older patients.

3-Methylmethcathinone (3-MMC) Poisonings: Acute Clinical Toxicity and Time Trend Between 2013 and 2021 in the Netherlands.

STUDY OBJECTIVE: The synthetic cathinone 3-methylmethcathinone (3-MMC, or metaphedrone) has recently gained popularity. We studied the numbers of 3-MMC poisonings over time and the clinical effects following poisonings with 3-MMC. METHODS: We performed a retrospective study on the numbers of self-reported 3-MMC poisonings to the Dutch Poisons Information Center (DPIC) from 2013 to June 2021. For poisonings reporting 3-MMC only, the symptoms were extracted and the Poisoning Severity Score (PSS) was determined. From 2016 to June 2019, a prospective cohort study on poisonings reporting only 3-MMC was performed, in which details on the clinical courses were collected through telephone interviews. RESULTS: From 2013 to June 2021, the DPIC was consulted on 184 3-MMC poisonings. The number of poisonings increased from 1 in 2013 to 70 in the first half of 2021. In 84 poisonings with only 3-MMC (46%), sympathomimetic symptoms were commonly reported, including tachycardia (n=29, 35%), hypertension (n=17, 20%), and agitation (n=16, 19%). The initial PSS was usually minor (n=37, 44%) to moderate (n=39, 46%). Five patients (6%) experienced severe effects, including 3 patients experienced severe hypertension (systolic blood pressure >180 mmHg; n=3) and nonfatal cardiac arrest (n=1). Sympathomimetic symptoms (n=8) were also reported in the prospective cohort study. The percentage of moderate poisonings increased (n=6, 75%), and 1 (13%) severe poisoning was observed. Analytical confirmation of 3-MMC exposure was performed in 2 cases. CONCLUSION: The number of 3-MMC poisonings reported to the DPIC has increased over time. Most poisonings with 3-MMC resulted in moderate toxicity and involved sympathomimetic effects, while severe effects were observed in 5 cases.

Pregabalin poisoning: Evaluation of dose-toxicity relationship.

CONTEXT: Pregabalin poisoning is mostly benign, although coma and convulsions occasionally occur. AIM: To determine the dose-toxicity relationship of pregabalin. METHODS: Dose-toxicity data of isolated pregabalin poisonings were collected from (1) a prospective study performed by the Dutch Poisons Information Centre (4 April 2014 to 4 October 2016) and from (2) case reports and case series reported in literature. Poisonings were graded using the Poisoning Severity Score (PSS) and the relationship between dose (mg kg-1 ) and PSS was evaluated. RESULTS: In our study (n = 21 patients), the most commonly observed symptoms were drowsiness (62%), confusion (29%) and apathy (24%). PSS was none in three (14%), minor in 15 (71%), and moderate in three patients (14%). Most case series also reported a PSS of none to minor in the majority of poisonings (69-100%). For 34 individual patients (21 from our study and 13 from literature), detailed data on dose and clinical course were available to examine the dose-toxicity relationship. The median dose was significantly lower in the PSS none-minor group ("benign") (8.6 mg kg-1 , interquartile range (IQ25-75) 5.0-17.6 mg kg-1 ) than in the PSS moderate-severe group ("significant toxicity") (46.7 mg kg-1 , IQ25-75 21.3-64.3 mg kg-1 ); estimate of the median difference = 27.3 mg kg-1 (95% confidence interval (CI): 10-48.6). CONCLUSIONS: In general, higher pregabalin doses result in more severe poisonings. Below 20 mg kg-1 the majority of patients (83%) only suffer from mild poisoning. However, large interindividual differences exist in pregabalin-induced toxicity. Therefore, pre-hospital triage should not only include pregabalin dose, but also underlying illnesses, co-exposures and reported symptoms.

A quarter of admitted poisoned patients have a mild poisoning and require no treatment: An observational study.

BACKGROUND: Poisoned patients are frequently admitted following Emergency Department (ED) presentation, while the necessity of such admissions is hardly investigated. We determined the proportion and characteristics of poisoned patients who were admitted, but in retrospect had an uneventful admission. METHODS: For this observational cohort study, all patients presented to the ED of a Dutch University Hospital with various poisonings during a 1.5-year period (January 2015-July 2016) were included. The uneventfulness of admissions, defined as patients with a low Poisoning Severity Score (PSS) who received no treatment, was determined in retrospect. RESULTS: We included 417 patients who visited the ED for poisoning. 247 Patients were admitted: 30% to a general ward, 58% to a MCU, and 12% to the ICU. The poisoning severity scores of the admitted patients were none to mild in 38%, moderate to severe in 59%, and fatal in 2%. Upon admission, 60% of the patients received treatment. In retrospect, 77% of the admitted patients had a moderate, severe or fatal poisoning and/or required treatment. However, 23% of the admitted patients had a mild poisoning and required no treatment. This group involved younger patients (median age of 23 versus 42 years) and a higher proportion of patients reporting exposure to only one substance (65% versus 51%). CONCLUSIONS: The majority of poisoned patients presented to the ED was admitted, while in retrospect, a quarter of these admissions were uneventful. Predictive parameters should be sought to identify patients who can be sent home safely.

Fatalities, Cerebral Hemorrhage, and Severe Cardiovascular Toxicity After Exposure to the New Psychoactive Substance 4-Fluoroamphetamine: A Prospective Cohort Study.

STUDY OBJECTIVE: We study adverse health effects after use of the new psychoactive substance 4-fluoroamphetamine. METHODS: All patients who reported 4-fluoroamphetamine exposure and for whom the Dutch Poisons Information Center was consulted by their physician in 2016 were included in a prospective cohort study. The clinical course was investigated through telephone interviews with the physician and/or patient, using standardized questionnaires. 4-Fluoroamphetamine was analyzed in remaining drug material and biological samples with liquid and gas chromatography-mass spectrometry techniques. RESULTS: We included 45 patients, and follow-up with the physician and/or patient was performed in 33 cases. All patients experienced adverse effects after 4-fluoroamphetamine use. Severe toxicity was reported in 8 patients. In 5 of these patients, 4-fluoroamphetamine exposure was confirmed in biological specimens. Severe toxicity that was reported included 2 fatalities, 4 patients with cerebral hemorrhage (1 fatal), 2 patients with inverted Takotsubo's cardiomyopathy, 1 patient with myocardial infarction, 1 patient with acute heart failure, and an overall high prevalence of pronounced hypertension and tachycardia. CONCLUSION: Since the introduction of 4-fluoroamphetamine to the Dutch drug market in 2007, its use continues to increase, possibly because users perceive it as "ecstasy light" and thus relatively safe. However, the proportion of patients with severe toxicity after 4-fluoroamphetamine use is relatively large in our study population. Therefore, users should be warned about the risks of 4-fluoroamphetamine.

Methylphenidate intoxications in children and adults: exposure circumstances and evidence-based dose threshold for pre-hospital triage.

CONTEXT: Methylphenidate intoxications mostly have a relatively mild course, although serious complications can occur. OBJECTIVE: We aimed to characterize methylphenidate exposures and reassess our current dose threshold for hospital referral (2 mg/kg). METHODS: In a prospective follow-up study, we analysed 364 consecutive methylphenidate exposures that were reported to the Dutch Poisons Information Center. Patients and/or physicians were surveyed by telephone using standardized questionnaires. Three physicians independently scored the observed severity of the intoxication of each patient as 'no/mild' (observation at home) or 'moderate/severe' (hospital referral necessary). RESULTS: Unintentional exposures (40%) mostly occurred at home involving the patients' own medication or those from a family member. Compared to unintentionally exposed patients, intentionally exposed patients were exposed to relatively high methylphenidate doses (3.1 vs 1.6 mg/kg), more often used immediate release methylphenidate formulations (62 vs 34%) and more frequently had concomitant exposures (71 vs 17%). Severe symptoms like convulsions or coma were reported only in patients with concomitant exposures. Following exposure to methylphenidate only (i.e. no concomitant exposures), the most commonly reported symptoms were dry mucosa, headache, agitation, sleepiness and tachycardia. Our results show that the reported methylphenidate dose is predictive of the observed severity of the intoxication and can therefore aid in pre-hospital triage. CONCLUSION: We increased our current dose threshold for hospital referral from 2 to 3 mg/kg. In addition, we will refer patients at lower doses when clinical symptoms indicate the need for hospital referral. Application of this new dose threshold optimizes triage, thereby reducing unnecessary hospital referral and thus costs, without jeopardising patient safety.

Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug-drug interactions.

Clinical outcome following 3,4-methylenedioxymethamphetamine (MDMA) intake ranges from mild entactogenic effects to a life-threatening intoxication. Despite ongoing research, the clinically most relevant mechanisms causing acute MDMA-induced adverse effects remain largely unclear. This complicates the triage and treatment of MDMA users needing medical care. The user's genetic profile and interactions resulting from polydrug use are key factors that modulate the individual response to MDMA and influence MDMA pharmacokinetics and dynamics, and thus clinical outcome. Polymorphisms in CYP2D6, resulting in poor metabolism status, as well as co-exposure of MDMA with specific substances (e.g. selective serotonin reuptake inhibitors (SSRIs)) can increase MDMA plasma levels, but can also decrease the formation of toxic metabolites and subsequent cellular damage. While pre-exposure to e.g. SSRIs can increase MDMA plasma levels, clinical effects (e.g. blood pressure, heart rate, body temperature) can be reduced, possibly due to a pharmacodynamic interaction at the serotonin reuptake transporter (SERT). Pretreatment with inhibitors of the dopamine or norepinephrine reuptake transporter (DAT or NET), 5-HT(2A) or α-ß adrenergic receptor antagonists or antipsychotics prior to MDMA exposure can also decrease one or more MDMA-induced physiological and/or subjective effects. Carvedilol, ketanserin and haloperidol can reduce multiple MDMA-induced clinical and neurotoxic effects. Thus besides supportive care, i.e. sedation using benzodiazepines, intravenous hydration, aggressive cooling and correction of electrolytes, it is worthwhile to investigate the usefulness of carvedilol, ketanserin and haloperidol in the treatment of MDMA-intoxicated patients.

Methamphetamine, amphetamine, MDMA ('ecstasy'), MDA and mCPP modulate electrical and cholinergic input in PC12 cells.

Reversal of the dopamine (DA) membrane transporter is the main mechanism through which many drugs of abuse increase DA levels. However, drug-induced modulation of exocytotic DA release by electrical (depolarization) and neurochemical inputs (e.g., acetylcholine (ACh)) may also contribute. We therefore investigated effects of methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine (mCPP) (1-1000 µM) on these inputs by measuring drug-induced changes in basal, depolarization- and ACh-evoked intracellular calcium concentrations ([Ca(2+)](i)) using a dopaminergic model (PC12 cells) and Fura 2 calcium imaging. The strongest drug-induced effects were observed on cholinergic input. At 0.1mM all drugs inhibited the ACh-evoked [Ca(2+)](i) increases by 40-75%, whereas ACh-evoked [Ca(2+)](i) increases were nearly abolished following higher drug exposure (1mM, 80-97% inhibition). Additionally, high MDMA and mCPP concentrations increased basal [Ca(2+)](i), but only following prior stimulation with ACh. Interestingly, low concentrations of methamphetamine or amphetamine (10 µM) potentiated ACh-evoked [Ca(2+)](i) increases. Depolarization-evoked [Ca(2+)](i) increases were also inhibited following exposure to high drug concentrations, although drugs were less potent on this endpoint. Our data demonstrate that at high drug concentrations all tested drugs reduce stimulation-evoked increases in [Ca(2+)](i), thereby probably reducing dopaminergic output through inhibition of electrical and cholinergic input. Furthermore, the increases in basal [Ca(2+)](i) at high concentrations of MDMA and mCPP likely increases dopaminergic output. Similarly, the increases in ACh-evoked [Ca(2+)](i) upon cholinergic stimulation following exposure to low concentrations of amphetamines can contribute to drug-induced increases in DA levels observed in vivo. Finally, this study shows that mCPP, which is regularly found in ecstasy tablets, is the most potent drug regarding the investigated endpoints.

A single session of resistance exercise induces oxidative damage in untrained men.

PURPOSE: During exercise, the production of reactive oxygen and nitrogen species significantly increases. The aim of the present study was to investigate the effects of a single session of resistance exercise on antioxidant capacity, oxidative damage, and inflammation. METHODS: Muscle biopsies, urine, and blood samples were collected from seven healthy men before and after a single bout of resistance exercise. RESULTS: A single session of resistance exercise was found to induce oxidative damage, as shown by a 40% increase in the concentration of urinary F2alpha-isoprostanes (P < 0.05). Total antioxidant capacity of plasma increased 16% (P < 0.05). This increase seemed to be predominantly attributable to an increase in plasma uric acid concentrations of 53% (P < 0.05). Similar to uric acid, but to a relatively much smaller extent, vitamin C and vitamin E levels in plasma were also elevated (P < 0.05). Moreover, the erythrocyte glutathione (GSH) [corrected] concentration increased 47% during exercise (P < 0.05). Also in skeletal muscle, uric acid levels were found to increase after exercise (P < 0.05). Moreover, 30 min after exercise, skeletal muscle glutathione S-transferase (GST) and glutathione reductase activity increased 28 and 42%, respectively (P < 0.05). Skeletal muscle reduced GSH [corrected] and GSH [corrected] disulphide (GSSG) concentrations were not affected by exercise. The Nuclear Factor kappa B (NF-kappaB) activity in peripheral blood mononuclear cells (PBMC) was not increased by exercise, indicating that a NF-kappaB-mediated inflammatory response does not occur. CONCLUSION: We conclude that a single session of resistance exercise induces oxidative damage despite an adaptive increase in antioxidant capacity of blood and skeletal muscle.

New insights into controversies on the antioxidant potential of the olive oil antioxidant hydroxytyrosol.

In the present study, the antioxidant profile of olive oil antioxidants was investigated. Hydroxytyrosol and oleuropein are potent scavengers of hydroxyl radicals (OH*), peroxynitrite (ONOOH), and superoxide radicals (O(2)*(-)). Homovanillic alcohol, one of the main metabolites of hydroxytyrosol, and tyrosol are less potent scavengers of these reactive species. None of the olive oil antioxidants are good hypochlorous acid (HOCl) or hydrogen peroxide (H(2)O(2)) scavengers. Hydroxytyrosol efficiently protects against LDL oxidation in vitro and in vivo. However, no protective effect of hydroxytyrosol is usually demonstrated ex vivo against the oxidation of LDL isolated from humans after hydroxytyrosol consumption. The present study shows that this controversy is due to the isolation of LDL, which greatly reduces the protective effect of hydroxytyrosol against LDL oxidation. Hydroxytyrosol is an efficient scavenger of several free radicals. The physiological relevance of the high intrinsic antioxidant activity of hydroxytyrosol is illustrated by its protection against LDL oxidation.

Effect of sex on the cardiovascular response to adrenaline in humans.

Cardiovascular responsiveness to stress conditions differs between men and women. It is not known to what extent this observation is explained by differences in the release of stress hormones like adrenaline, or by differences in the response to adrenaline. Therefore, we quantified the hemodynamic response to infusion of adrenaline (0.04, 0.06, and 0.08 microg x kg(-1) x min(-1) for 20 minutes each) in 8 healthy men and 8 healthy premenopausal women. Arterial plasma adrenaline levels were measured before and after infusion. Heart rate and intra-arterial blood pressure were monitored throughout the experiment. Arterial plasma adrenaline levels increased similarly in both sexes. There was a larger increase in systolic blood pressure in women compared with men (17.6 +/- 2.8 versus 5.1 +/- 3.1 mm Hg, P < 0.01). In contrast, men showed a larger increase in heart rate compared with women (20.3 +/- 1.4 versus 11.2 +/- 2.8 bpm, P < 0.01). In conclusion, these data suggest that the cardiovascular response to adrenaline is predominantly alpha-adrenergic in premenopausal women, and predominantly beta-adrenergic in age-matched men.

Antecedent adrenaline attenuates the responsiveness to but not the release of counterregulatory hormones during subsequent hypoglycemia.

Hypoglycemia unawareness is thought to be the consequence of recurrent hypoglycemia, yet the underlying mechanism is still incompletely understood. The aim of the present study was to determine the role of antecedent elevated adrenaline in the pathogenesis of hypoglycemia unawareness. Sixteen healthy volunteers (eight of either sex) participated in two experiments, performed in random order and at least 3 wk apart. During the morning, three consecutive doses of 0.04, 0.06, and 0.08 microg.kg(-1).min(-1) of adrenaline or matching placebo (normal saline) were infused for the total duration of 1 h. Three hours later, a hyperinsulinemic (360 pmol.m(-2).min(-1)) two-step hypoglycemic (5.0-3.5-2.5 mmol.liter(-1)) clamp study was performed. During hypoglycemia, hypoglycemic symptoms, counterregulatory hormones, cardiovascular responses, and cognitive function were monitored. Hypoglycemia induced similar responses of autonomic and neuroglycopenic symptoms, counterregulatory hormones, and lengthening in reaction time on the choice reaction time task, irrespective of antecedent infusions. However, prior adrenaline was associated with higher exogenous glucose requirements at hypoglycemic nadir (10.1 +/- 1.3 vs. 7.3 +/- 1.3 micromol.kg(-1).min(-1), P = 0.017), an attenuated hypoglycemia-induced fall in blood pressure (mean arterial pressure, -13 +/- 2 vs. -8 +/- 2 mm Hg, P = 0.006), and preserved cognitive function as assessed by the symbol digit test during hypoglycemia, when compared with prior placebo. We conclude that elevated adrenaline attenuates the responsiveness to, but not the release of counterregulatory hormones during subsequent hypoglycemia. As such, adrenaline's role in the development of hypoglycemia unawareness is limited.