Julio Pallavicini

Increased number of circulating endothelial cells and plasma markers of endothelial damage in chronic cocaine users.

BACKGROUND Cocaine use has been related with the development of accelerated atherosclerosis and with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood, although thrombus formation and altered vascular function are prominent findings. OBJECTIVES Our aim was to evaluate markers of endothelial dysfunction in chronic cocaine consumers before and after drug withdrawal. PATIENTS/METHODS We determined circulating endothelial cells (CECs) and plasma levels of stromal cell-derived factor-1 (SDF-1), monocyte chemotactic protein-1(MCP-1), soluble intracellular adhesion molecule (sICAM), high-sensitivity C reactive protein (hsCRP) and endothelin-1(ET-1), in DSM-IV cocaine addicts at baseline and after one month of cocaine abstinence. RESULTS Cocaine users showed a strikingly higher numbers of CEC (62.35 ± 18.4 vs 8.25 ± 13.8 CEC/mL) and significantly elevated plasma levels for all the markers evaluated as compared to the control group. After cocaine withdrawal, patients improved SDF-1, ET-1, hsCRP and sICAM levels. However, CEC number and MCP-1 plasma levels remained significantly elevated. All the results were adjusted for blood levels of cholesterol and triglycerides and for smoking habit. CONCLUSIONS Our results demonstrated that chronic cocaine consumption alters several functions of the endothelium towards a pro-thrombotic condition and that some of those functions remain abnormal even after short-term drug withdrawal. These observations support the notion that endothelial dysfunction may play a key role in the pathogenesis of ischemic vascular disease observed in cocaine abusers.

Platelet activation in chronic cocaine users: effect of short term abstinence.

Cocaine abuse increases the risk of cardiac and cerebrovascular events, such as myocardial infarction and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation has been observed. The aim of this study was to investigate the existence of platelet activation and the effect of short-term abstinence in chronic cocaine consumers. We studied 23 cocaine dependent individuals (aged 20–54 years) who met DSM-IV criteria for cocaine dependence and 20 controls. Samples were obtained at baseline, within 72 h of last drug exposure and after 4 weeks of controlled abstinence. Monocyte-platelet aggregates (MPA) were measured by flow cytometry. Plasma levels of soluble CD40L (sCD40L), Neutrophil-Activating Peptide-2 (NAP-2) and regulated on activation normal T cells expressed and secreted (RANTES) were determined by ELISA. Levels of MPA, sCD40L, NAP-2 and RANTES were significantly higher (all p < 0.05) in cocaine addicts compared to controls at baseline. All the parameters returned to values similar to the control group after 4-weeks’ abstinence. Levels of sCD40L and RANTES were associated with an index of intensity of drug consumption (p < 0.02). Our results demonstrate that cocaine use induces platelet activation which is a prominent finding after recent consumption. The persistence over time of this condition may contribute not only to acute thrombotic complications but also to the development of early-onset atherosclerotic process observed in cocaine abusers.

Changes in Regional Cerebral Blood Flow Are Associated With Endothelial Dysfunction Markers in Cocaine-dependent Patients Under Recent Abstinence

Objectives:Cocaine is a known risk factor for several vascular ischemic events. The underlying mechanisms leading to the complications are not fully understood, although thrombus formation and accelerated atherosclerosis are prominent findings. Evidence of endothelial dysfunction (ED), a key phenomenon in the pathogenesis of atherogenesis, has been demonstrated in cocaine-dependent individuals. Abnormal regional cerebral blood flow (rCBF) is a common finding among chronic cocaine users. The aim of this study was to evaluate whether brain perfusion changes were associated with ED markers in cocaine-dependent individuals. Methods:Circulating endothelial cells (CECs), soluble intercellular cell adhesion molecule, and the chemokine regulated on activation normal T cells expressed and secreted were measured in 27 DSM-IV (Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition) cocaine-dependents patients. Regional cerebral blood flow was assessed using single-photon emission computed tomography at baseline (after recent cocaine consumption) and after 4 weeks of strict abstinence under standard benzodiazepine or antipsychotic therapy. We used statistical parametric mapping analysis to evaluate the covariates. Results:Endothelial cell damage/activation markers were significantly higher in cocaine-dependent individuals after recent consumption and were reduced after 1-month abstinence (P < 0.05). Global rCBF exhibited no significant difference between baseline and after abstinence. When regional perfusion was analyzed in association with ED covariates, significant differences were observed in bilateral cortical areas, including the limbic lobes. Conclusions:We demonstrated an association between systemic ED markers and rCBF in cocaine-dependent patients. These findings suggest that vascular injury may play a role in the pathogenesis of abnormal rCBF.

Descripción de los hallazgos en el perfil lipídico y proteico de pacientes dependientes a cocaína, en abstinencia reciente

BACKGROUND Chronic cocaine users develop multiple potentially lethal ischemic vascular complications associated with accelerated atherosclerosis. AIM To assess biochemical and lipid profiles among cocaine dependent subjects in recent abstinence. MATERIAL AND METHODS A blood sample to measure blood count, biochemical and lipid profiles was obtained from 78 patients aged 19 to 53 years (78% males) who complied with DSM-IV criteria for cocaine dependency. Laboratory results were compared with a group of normal subjects. RESULTS All cases had positive urinary cocaine, with a mean consumption lapse of 7.6 years. The frequency of smoking was higher in cases. Dependent males had higher body mass index than controls. Compared to controls, dependent females had significantly higher triglyceride (TG) levels and lower HDL cholesterol. Therefore the relation total/HDL cholesterol was higher (p = 0.0365). Dependent males had higher TG levels than their normal counterparts. Dependent subjects consuming cocaine base-paste had higher TG levels. Total proteins, albumin, urea and blood urea nitrogen were lower in dependent subjects. Among males, serum creatinine was lower and blood urea was positively correlated with the daily amount of cocaine use (p = 0.03). After a month of strict abstinence, lipid profile was repeated in 27 patients and remained unchanged. CONCLUSIONS Chronic cocaine use was associated with higher TG in both genders and lower HDL cholesterol in women when compared with a group of healthy counterparts.Background: Chronic cocaine users develop multiple potentially lethal ischemic vascular complications associated with accelerated atherosclerosis. Aim: To assess biochemical and lipid profiles among cocaine dependent subjects in recent abstinence. Material and methods: A blood sample to measure blood count, biochemical and lipid profiles was obtained from 78 patients aged 19 to 53 years (78% males) who complied with DSM –IV criteria for cocaine dependency. Laboratory results were compared with a group of normal subjects. Results: All cases had positive urinary cocaine, with a mean consumption lapse of 7.6 years. The frequency of smoking was higher in cases. Dependent males had higher body mass index than controls. Compared to controls, dependent females had significantly higher triglyceride (TG) levels and lower HDL cholesterol. Therefore the relation total/HDL cholesterol was higher (p=0.0365). Dependent males had higher TG levels than their normal counterparts. Dependent subjects consuming cocaine base-paste had higher TG levels. Total proteins, albumin, urea and blood urea nitrogen were lower in dependent subjects. Among males, serum creatinine was lower and blood urea was positively correlated with the daily amount of cocaine use (p=0.03). After a month of strict abstinence, lipid profile was repeated in 27 patients and remained unchanged. Conclusions: Chronic cocaine use was associated with higher TG in both genders and lower HDL cholesterol in women when compared which a group of healthy counterparts.

Efecto de la inhibición de la síntesis de angiotensina II en el consumo de alcohol

BACKGROUND Central renin-angiotensin system modulates alcohol intake and inhibition of angiotensin converting enzyme reduces ethanol consumption in rats, and may be potentially useful in the treatment of alcoholism. AIM To study the effect of captopril on alcohol intake, both in humans and animals . MATERIAL AND METHODS In a double-blind, placebo-controlled clinical study, 15 alcoholics who met DSM-IV criteria were randomized to receive captopril 100 mg/day or placebo for 12 weeks. In the experimental study, daily consumption of ethanol (10% v/v), water and solid food was assessed in 12 male Wistar rats before and after the intraperitoneal administration of captopril 50 mg/kg/day. RESULTS In alcoholics, mean weekly standard alcoholic drink consumption was not different during captopril treatment or placebo. However, both groups had a significantly lower intake than during baseline. Days of abstinence increased and days of drunkeness decreased in the group receiving captopril, when compared with baseline but not with placebo. Craving was significantly reduced by captopril when compared with placebo. In rats, captopril reduced not only alcohol consumption but also water and food intake. CONCLUSIONS Captopril decreases alcohol intake in rats and this effect is not specific for ethanol. Captopril did not alter alcohol consumption in alcoholics when compared with placebo but reduced craving.