Smoke-derived nitric oxide and vascular prostacyclin are unable to counteract the platelet effect of increased thromboxane formation in healthy female smokers

Summary. The incidence of cigarette smoking tends to be higher in women, justifying directed studies on smoke-related mechanisms of cardiovascular disorder in females. Platelet activity plays an important etiological role in several settings of cardiovascular disease. Cigarette smoking facilitates platelet formation of proaggregatory thromboxane A₂. However, cigarette smoke contains nitric oxide (NO), which has antiplatelet activity. Furthermore, the formation of anti-aggregatory prostacyclin (PGl₂) may be higher in smokers than in non-smokers. Hence, the concerted action of NO and PGI₂ on platelet activity in smoking females is important to elucidate. The metabolites of TxA₂, NO, and PGI₂, as well as cyclic guanosine 3′:5′-monophosphate (cGMP; second messenger for NO in the platelets) and cyclic adenosine 3′:5′-monophosphate (cAMP; second messenger for PGI₂ in the platelets), were analysed in 23 healthy female smokers (daily consumption 11–20 cigarettes per day) and in 26 matched non-smokers. The urinary excretion of 2,3-dinor TxB₂ (metabolite of TxA₂) was considerably higher in smokers than in non-smokers (177 vs. 72 pg/mg creatinine, respectively; P < 0.001). Plasma and urinary levels of nitrate (metabolite of inhaled NO) did not differ between the groups. Plasma and urinary cGMP were slightly increased (252 vs. 193 nmol/L; P < 0.05 and 0.63 vs. 0.51 μmol/24 h; P < 0.05, respectively) in smokers compared to non-smokers, while platelet cGMP was lower in smokers than in non-smokers (81 vs. 10.3 pmol/10⁶ platelets, respectively; P < 0.05).The urinary excretion of 2,3-dinor-6-keto-PGF_1a (metabolite of PGI₂) did not differ between the groups. Platelet or urinary cAMP did not differ between the groups either, while plasma cAMP was lower in smokers than in non-smokers (19.2 vs. 26.2 nmol/1, respectively; P < 0.001). In healthy female smokers NO is not absorbed from the inhaled smoke, and endothelial PGI₂ formation is not enhanced to counterbalance the increased platelet formation of proaggregatory TxA₂.     

2,3-Dinor metabolites of thromboxane A2 and prostacyclin in urine from healthy human subjects: diurnal variation and relation to 24h excretion.

1. Urinary levels of the 2,3-dinor metabolites of thromboxane A2 (2,3-dinor-thromboxane A2, Tx-M) and prostacyclin (2,3-dinor-6-keto-prostaglandin F1 alpha, PGI-M) are frequently analysed as indices of platelet and endothelial activity and interaction in vivo. Despite this, little is known about the possible diurnal variations in urinary Tx-M and PGI-M in healthy human subjects, and how the urinary levels of Tx-M and PGI-M in single samples reflect their respective 24 h excretion rates. We addressed this by determining Tx-M, PGI-M and creatinine in consecutive portions of urine collected during 24 h in 15 healthy non-smoking subjects. 2. The total 24 h excretion of Tx-M and PGI-M did not differ between men (223 +/- 31 and 132 +/- 27 ng, respectively) and women (215 +/- 44 and 127 +/- 29 ng, respectively). Neither the excretion of Tx-M nor that of PGI-M displayed any significant diurnal variation. 3. The excretion of Tx-M during a 3 h period and the Tx-M/creatinine ratio in a urine sample accurately reflected the 24 h excretion of Tx-M (correlation coefficient ranges 0.74-0.94 and 0.74-0.86, respectively). The excretion of PGI-M during a 3 h period and the PGI-M/creatinine ratio in a urinary sample were accurate measures of 24 h excretion of PGI-M (correlation coefficient ranges 0.76-0.94 and 0.72-0.83, respectively). Urinary Tx-M and PGI-M expressed as simple concentrations were poor indices of their respective 24 h excretion. 4. We conclude that time-related excretions of Tx-M and PGI-M may be the best indices ex vivo of the cardiovascular formation of thromboxane A2 and prostacyclin, but that urinary creatinine-related concentrations of Tx-M and PGI-M in a urine sample are accurate measures as well.     

Non-invasive assessment of the cardiovascular eicosanoids, thromboxane A2 and prostacyclin, in randomly sampled males, with special reference to the influence of inheritance and environmental factors

1. We studied, in a random sample of 385 nonsmoking men born in 1968-1969 and 31 men born in 1913 or 1923, whether inheritance and environmental factors influenced platelet activity and vessel wall prostacyclin formation, as reflected non-invasively by the urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 (2,3-dinor-thromboxane B2, Tx-M) and prostacyclin (2,3-dinor-6-keto-prostaglandin F1 alpha, PGI-M), respectively. 2. Fathers of young men with high platelet activity did not excrete more Tx-M than fathers of young men with low platelet activity. Men born in 1913 or 1923 displayed higher Tx-M (563 versus 128 pg/mg of creatinine, P less than 0.001) and PGI-M (163 versus 130 pg/mg of creatinine, P less than 0.01) excretion than those born in 1968-1969. Excretion of both Tx-M and PGI-M was correlated to the urinary output of noradrenaline and adrenaline. 3. Well-trained subjects did not differ in their excretion of Tx-M or PGI-M from those who did not exercise regularly. A recent acute infection was also unrelated to the excretion of Tx-M or PGI-M. PGI-M excretion was, however, significantly correlated to Tx-M excretion (r = 0.51, P less than 0.001). 4. This study provides the first non-invasive evidence that advancing age and sympathoadrenal tone are positively correlated to platelet activity in randomly sampled men, and that paternal inheritance, physical fitness and recent infection lack correlation to platelet activity.     

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man

To assess the pharmacologic effects of aspirin on endogenous prostacyclin and thromboxane biosynthesis, 2,3-dinor-6-keto PGF1 alpha (PGI-M) and 2,3-dinor-thromboxane B2 (Tx-M) were measured in urine by mass spectrometry during continuing administration of aspirin. To define the relationship of aspirin intake to endogenous prostacyclin biosynthesis, sequential urines were initially collected in individuals prior to, during, and subsequent to administration of aspirin. Despite inter- and intra-individual variations, PGI-M excretion was significantly reduced by aspirin. However, full mass spectral identification confirmed continuing prostacyclin biosynthesis during aspirin therapy. Recovery of prostacyclin biosynthesis was incomplete 5 d after drug administration was discontinued. To relate aspirin intake to indices of thromboxane biosynthesis and platelet function, volunteers received 20 mg aspirin daily followed by 2,600 mg aspirin daily, each dose for 7 d in sequential weeks. Increasing aspirin dosage inhibited Tx-M excretion from 70 to 98% of pretreatment control values; platelet TxB2 formation from 4.9 to 0.5% and further inhibited platelet function. An extended study was performed to relate aspirin intake to both thromboxane and prostacyclin generation over a wide range of doses. Aspirin, in the range of 20 to 325 mg/d, resulted in a dose-dependent decline in both Tx-M and PGI-M excretion. At doses of 325-2,600 mg/d Tx-M excretion ranged from 5 to 3% of control values while PGI-M remained at 37-23% of control. 3 d after the last dose of aspirin (2,600 mg/d) mean Tx-M excretion had returned to 85% of control, whereas mean PGI-M remained at 40% of predosing values. Although the platelet aggregation response (Tmax) to ADP ex vivo was inhibited during administration of the lower doses of aspirin the aggregation response returned to control values during the final two weeks of aspirin administration (1,300 and 2,600 mg aspirin/d) despite continued inhibition of thromboxane biosynthesis. These results suggest that although chronic administration of aspirin results in inhibition of endogenous thromboxane and prostacyclin biosynthesis over a wide dose range, inhibition of thromboxane biosynthesis is more selective at 20 than at 2,600 mg aspirin/d. However, despite this, inhibition of platelet function is not maximal at the lower aspirin dosage. Doses of aspirin in excess of 80 mg/d resulted in substantial inhibition of endogenous prostacyclin biosynthesis. Thus, it is unlikely that any dose of aspirin can maximally inhibit thromboxane generation without also reducing endogenous prostacyclin biosynthesis. These results also indicate that recovery of endogenous prostacyclin biosynthesis is delayed following aspirin administration and that the usual effects of aspirin on platelet function ex vivo may be obscured during chronic aspirin administration in man.     

Excretion of thromboxane A2 and prostacyclin metabolites during treadmill exercise in patients with intermittent claudication

Platelet activation, with subsequent formation of thromboxane A₂ (TxA₂), is thought to play a role in the development of arterial occlusion. In patients with severe atherosclerosis of the lower limbs, characterized by leg ulcers and rest pain, the basal formation of TxA₂ and prostacyclin (PGI₂) is increased. Corresponding data in patients with more moderate atherosclerosis of the lower limbs have not been reported. Since the capacity to physical exercise is not blunted in such patients proper evaluation of their TxA₂-PGI₂ synthesis should comprise not only assessment of the basal formation, but also TxA₂/PGI₂ biosynthesis during conditions of elevated cardiovascular activity. To address this, we analysed these eicosanoids in patients with a history of intermittent claudication. Urinary dinormetabolites of TxB₂ and PGI₂ (Tx-M and PGI-M, respectively) were estimated by gas chromatography/negative ion-chemical ionization mass spectrometry in samples collected prior to, during and immediately after 20 min of severe treadmill exertion. The basal excretion of Tx-M was 105 ± 26 pg/mg creatinine. It was not changed during exercise, but increased to 176 ± 48 pg/mg creatinine (P<0·05) during the recovery. The basal excretion of PGI-M was 142 ± 25 pg/mg creatinine. The PGI-M response to exercise varied from no change at all to a 30-fold increase, without any obvious correlation to experienced leg pain, walking distance or other recorded variables. During the recovery period the outflow of PGI-M was significantly higher than at rest (482 ± 145 pg/mg creatinine; P<0·01). We conclude that in patients with intermittent claudication due to atherosclerosis (1) platelet activation does not occur during the course of the exercise, and (2) vascular prostacyclin formation can be dissociated from of TxA₂ synthesis. The observed increase in PGI-M in some of the patients is suggested to reflect tissue ischaemia induced by the lack of adequate hyperaemia during exercise.     

Cigarette smoking and urinary excretion of markers for platelet/vessel wall interaction in healthy women.

1. Cigarette smoking is known to increase the risk of cardiovascular disease in both men and women. Experimental and epidemiological studies have demonstrated that cigarette smoking is associated with several indices of increased platelet activation and platelet/vessel wall interaction in men. The aim of the present study was to test the hypothesis that cigarette smoking is linked to an increased platelet activity in women also. 2. In 26 healthy smoking and non-smoking women (age 21-49 years) the urinary excretion of the thromboxane A2 metabolite 2,3-dinor-thromboxane B2 (an index of platelet activation) and of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha (an index of platelet/vessel wall interaction) were analysed by g.c.-m.s. in samples collected on days 3, 10 and 20 of their respective menstrual cycles. 3. The urinary excretion of 2,3-dinor-thromboxane B2 did not vary significantly during the menstrual cycle, either in the smokers or in the non-smokers. It was consistently higher (P less than 0.004) in the group of smokers (average of day 3, 10 and 20, 395 +/- 61 pg/mg of creatinine; mean +/- SEM) than in the group of non-smokers (average 188 +/- 22 pg/mg of creatinine). 4. The urinary excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha did not differ between the groups on any of the days studied (average on days 3, 10 and 20 in the smokers and non-smokers was 281 +/- 50 and 227 +/- 30 pg/mg of creatinine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thromboxane metabolite excretion in patients with hand-arm vibration syndrome

SUMMARY. As chronic exposure to hand-held vibrating tools may cause endothelial injury, a subsequent sustained platelet activation with the increased release of vasocon-stricting thromboxane A₂ (TxA₂) could be of pathophysiological importance in vibration-induced Raynaud's phenomenon. Therefore, the aim of this study was to elucidate whether or not hand-arm vibration syndrome is accompanied by increased endogenous TxA₂ biosynthesis. The study involved 64 men, aged 23–61 years, stratified according to the exposure to vibrating tools, the presence of Raynaud's phenomenon, and smoking habit. Forty of them were car mechanics and 24 were age-matched healthy volunteers who served as controls. The assessment of platelet TxA₂ formation in vivo was performed by quantification of the urinary excretion of its major metabolite, 2,3-dinor-thromboxane B₂ (2,3-dinor-TxB₂), employing gas chromatography - mass spectrometry. The average urinary excretion rate of 2,3-dinor-TxB₂ in patients with Raynaud's phenomenon was 296±42 pg/mg creatinine and did not differ significantly from the corresponding values in controls (328±62 pg/mg creatinine) or individuals exposed to vibrating tools, but without any signs of vasospastic disease (232±29 pg/mg creatinine). The only statistically significant difference was found between smokers and non-smokers (P < 0.001), a finding confirming the existence of chronic platelet dysfunction in cigarette smokers. The present data indicate that chronic exposure to vibrating tools, with or without Raynaud's phenomenon, is not associated with an enhanced platelet function as monitored by the urinary excretion of 2,3-dinor-TxB₂. Hence, a possible vibration-induced vascular injury does not seem to provide a stimulus sufficient to induce a persistent platelet activation.     

Platelet aggregability in smoking and non-smoking subjects

Summary. The hypothesis was investigated that the arachidonic acid (AA) system has a different impact on platelet function in smoking compared to non-smoking subjects. Arterial blood was sampled from smokers and non-smokers, and platelet-rich plasma (PRP) was prepared. There were no differences in sex and age distribution between the groups. One portion of the PRP was used to determine the lowest amount of AA required to induce platelet aggregation. In other portions the endogenous antiaggregatory (prostacyclin/PGI₂/-like) activity in the blood was determined, after reinforcing it with theophylline. There was no difference between smokers and non-smokers regarding the amount of AA required to induce platelet aggregation. In fresh PRP prepared from blood from non-smoking subjects theophylline (10^-4 M) induced a 12–17% inhibition of the ADP-induced aggregation of platelets, indicating the presence of endogenous sub-threshold concentrations of PGI₂, -like activity in their blood. The corresponding inhibition in fresh PGI₂ prepared from blood from smokers was significantly lower (4–7%), suggesting lower endogenous concentrations of PGI₂-like activity in their blood, or alternatively, decreased platelet sensitivity to the action of such activity. From these data we conclude that smokers differ from non-smokers with regard to their platelet function: platelet aggregability in response to AA is unaffected, while the endogenous anti-aggregatory power in the plasma is decreased. These observations may be of significance for the cardiovascular hazards connected with smoking.     

Cigarette smoking stimulates cysteinyl leukotriene production in man

Chronic cigarette smoking is an important risk factor for pulmonary and cardiovascular diseases. An increased production of cysteinyl leukotrienes has been shown in asthma and in cardiac ischaemia. The effect of cigarette smoking on cysteinyl leukotriene biosynthesis is, however, not known. Urinary leukotriene E₄ (LTE₄)was measured in 30 habitual smokers and in 30 non-smokers. In a further 12 non-smokers urinary LTE₄ excretion was assessed before and after smoking six cigarettes. In addition, the effect of transdermal nicotine on urinary LTE₄ excretion was studied in seven non-smokers. There was a close correlation (r = 0.92, P < 0.0001) between urinary excretion of LTE₄ and the number of cigarettes smoked daily by habitual smokers. Smoking six cigarettes within 12 h resulted in a significant (P = 0.0047), twofold increase in the mean individual LTE₄ excretion in non-smokers. Transdermal nicotine had no effect on LTE₄ excretion in non-smokers. In conclusion, cigarette smoke causes a dose-related increase in cysteinyl leukotriene production in habitual smokers. Some of the adverse effects of smoking may be related to an enhanced leukotriene synthesis.     

Formation of prostacyclin during administration of β1-selective and non-selective β-adrenergic antagonists in healthy humans

Summary. Vascular formation of prostacyclin is increased by propranolol in patients with essential hypertension. However the possible effect of β-adrenoceptor blocking drugs in healthy subjects is, however, not known. We studied this issue by analysis of the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-prostaglandin F_la during intake of a (β₁-selective (metoprolol) or a non-selective (propranolol) (3-adrenoceptor antagonist. After 14 days of metoprolol treatment (100 mg d^-1) the urinary excretion of PGI-M did not differ from control (253 ± 77 vs. 220 ± 33 pg mg^-1 creatinine, respectively). Five days of randomized cross-over treatment with propranolol (80 mg day^-1) or placebo did not affect urinary PGI-M significantly either (177 ± 11 vs. 202 ± 11 pg mg^-1 creatinine, respectively). Furthermore, a daily increasing dose of propranolol (80–480 mg) progressively lowered resting blood pressure and heart rate, but failed to influence urinary excretion of PGI-M. The data demonstrate that metoprolol and propranolol do not affect basal cardiovascular formation of prostacyclin in healthy subjects. Thus, the biosynthesis of prostacyclin does not appear to be regulated by p-adrenoceptor activity under normal conditions.     

Plasma noradrenaline and ageing: effects of smoking habits

Abstract. We tested the hypothesis that long-term smoking is responsible for increased plasma noradrenaline (NA) in elderly healthy subjects. Thirty-nine subjects were studied both at rest and during exercise: 10 young non-smokers (median age 24 years, range 21–33), 10 young smokers (30.5 years, 27–36), 10 elderly non-smokers (64 years, 52–75) and nine elderly smokers (62 years, 56–68). The young and elderly subjects had smoked for an average of 15 years and 46.8 years respectively. Plasma NA was significantly elevated in elderly long-term smokers compared with elderly non-smokers, young non-smokers and young smokers in both supine and sitting positions (supine: 1.06 ± 0.24 vs. 0.71 ± 0.22, 0.53 ± 0.12, and 0.70 ± 0.29 nmolL^-1 respectively; sitting: 3.01 ± 0.83 vs. 2.07 ± 0.77, 1.89 ± 0.52 and 2.25 ± 0.47 nmol L^-1 respectively). Plasma adrenaline did not differ among the groups. At submaximal exercise (60 W), plasma NA was significantly elevated in the elderly smokers compared with the other groups, owing to the elevated basal values. Increments in plasma NA at 60, 100 and 140 W were correlated with the relative exertion and not influenced by smoking. Plasma NA increased more in young subjects than in the elderly during maximal work load (21.7 ± 8.0 vs. 13.4 ± 5.4 nmol L^-1) and correlated with the peak O₂ uptake. Total blood volume was not different among the four groups and correlated inversely with basal plasma NA. It is concluded that long-term smoking may contribute to increased basal plasma NA concentrations and probably also increased sympathetic nerve activity in elderly healthy subjects, whereas smoking has little if any effect on plasma NA responses induced by exercise. Interindividual variability in basal plasma NA concentrations may in part be explained by differences in blood volume.     

Increased biosynthesis of thromboxane A2 by diabetic platelets

Abstract. Because ADP has been reported to produce a secondary wave of platelet aggregation in diabetic subjects, and since ADP is known to enhance normal platelet biosynthesis of pro-aggregating thromboxane A₂, we tested whether or not the reported increased sensitivity of diabetic platelets to ADP may also result in increased platelet biosynthesis of thromboxane A₂. To test this hypothesis, ¹⁴C-arachidonic acid (¹⁴C-AA) was incubated in vitro with washed human platelets' in the presence or absence of ADP. These studies included platelets isolated from thirty normal volunteers, twenty-six diabetic subjects with and without known vascular complications, eighteen non-diabetic pregnant females and fourteen pregnancy-induced diabetic females. Data from these studies demonstrated: (i) a significant increase in the capability of diabetic platelets in response to ADP to biosynthesize thromboxane A₂ from arachidonic acid when compared to platelets from normal controls (P < 0.001); (ii) a significant increase in thromboxane A₂ biosynthesis by platelets from pregnancy-induced diabetic subjects over nondiabetic pregnant females (P < 0.001); (iii) a two-fold increase in thromboxane A₂ biosynthesis by platelets from diabetic subjects with vascular complications when compared to those without vascular complications. Although our data also showed approximately a twofold increase in thromboxane A₂ biosynthesis by platelets from diabetic subjects with greater than 10 years of the disease when compared to diabetic subjects with less than 10 years, these latter results were, however, not statistically significant. Results from these studies suggest that a relationship may exist between the markedly increased ADP-induced platelet aggregation in diabetes mellitus and the vascular complications associated with this disease. Whether or not increased capacity of the diabetic platelet to biosynthesize pro-aggregating thromboxane A₂ in response to ADP or other pro-aggregating agents is per se a triggering factor in occlusive vascular diseases reported in diabetic subjects must await further studies.     

Altered skeletal muscle glucose transport and blood lipid levels in habitual cigarette smokers

We determined whether habitual cigarette smoking alters insulin-stimulated glucose transport and GLUT4 protein expression in skeletal muscle. Vastus lateralis muscle was obtained from 10 habitual cigarette smokers and 10 control subjects using an open muscle biopsy procedure. Basal 3-O-methylglucose transport was twofold higher (P > 0·01) in muscle from habitual smokers (0·05 ± 0·08 vs. 1·04 ± 0·19 μmol ml^?1 h^?1; controls vs. smokers respectively). Insulin (600 pmol l^?1) increased glucose transport 2·6-fold (P > 0·05) in muscle from control subjects, whereas no significant increase was noted in habitual smokers. Skeletal muscle GLUT4 protein expression was similar between the groups. FFA levels were elevated in the smokers (264 ± 49 vs. 748 ± 138 μmol l^?1 for control subjects vs. smokers; P < 0·05), and serum triglyceride levels were increased in the smokers (0·9 ± 0·2 vs. 2·3 ± 0·6 mmol l^?1 for control subjects vs. smokers; P < 0·05). Skeletal muscle carnitine palmitil (acyl) transferase activity was similar between the groups, indicating that FFA transport into the mitochondria was unaltered by cigarette smoking. In conclusion, cigarette smoking appears to have a profound effect on glucose transport in skeletal muscle. Basal glucose transport is markedly elevated, whereas insulin-stimulated glucose transport is impaired. These changes cannot be explained by altered protein expression of GLUT4, but may be related to increased serum FFA and triglyceride levels. These findings highlight the importance of identifying habitual cigarette smokers in studies aimed at assessing factors that lead to alterations in lipid and glucose homeostasis in people with non-insulin-dependent diabetes mellitus (NIDDM).     

Effects of cigarette smoking on short-term variability of blood pressure in smoking and non smoking healthy volunteers

The present trial was planned to study the effects of smoking on short-term variability of blood pressure and on haemodynamic parameters after an overnight cessation and after one day of repeated smoking in healthy cigarette smoking volunteers, compared to a control group of non-smokers who were not asked to smoke. 40 healthy male volunteers, 20 smokers and 20 non-smokers, participated in an open study with two period of measurements over a single day (morning and afternoon). Blood pressure and heart rate were measured using standard and finger recordings over 6 min before and 10 min after smoking one cigarette (in smokers only). During the two periods, smokers were asked to smoke 4 cm of a cigarette containing 1 mg of nicotine in 2 min, and a blood sample was taken for a plasma nicotine assay. In the smoking group, smoking the first cigarette of the day caused a significant increase of systolic blood pressure (+7%), diastolic blood pressure (+10%) and heart rate (+25%). The blood pressure variability in the frequency range of the Mayer waves (66-129 mHz) was increased after an overnight cessation of smoking in the smoking group in comparison to the non-smokers, and decreased significantly after the first cigarette of the day (7.1 +/- 4.0 to 3.2 +/- 1.8 mmHg2; P < 0.01). The changes observed in the afternoon after continuous smoking were significantly less important (3.8 +/- 1.9 to 3.2 +/- 1.9 mmHg2; NS). In the non-smoking group, the different parameters remained stable between the different measurements. These results suggest that an overnight cessation of smoking in smoking subjects is associated with a increase in sympathetic activity to the vascular system in the morning, which is released by smoking the first cigarette. This effect of smoking is reduced in the afternoon after a continuous nicotinic impregnation.     

Cigarettes smoking habit may reduce benefit from cetuximab-based treatment in advanced colorectal cancer patients

Background: NF-κB is one of the nuclear effectors of EGFR activation. There are reports showing that NF-κB expression and activity is enhanced after nicotine treatment. Some data demonstrated that NF-κB activation plays a role in the induction of resistance to cetuximab and irinotecan in advanced colorectal tumors. The aim of this study was to evaluate the effect of cigarette smoking on cetuximab efficacy in advanced colorectal cancer patients. Methods: We retrospectively analysed the smoking habits of 200 patients treated with a variety of anticancer regimens containing cetuximab for advanced colorectal cancer. All patients were irinotecan-resistant and received an oxaliplatin-based first line treatment. We divided our patient population as follows: no previous smoking habit, previous smokers (any number of cigarettes), current smokers of less of 10 cigarettes/day, current smokers of more than 10 cigarettes/day. Results: Out of 200 patients 58 declared a history of cigarette smoking, 108 patients never smoked and the remaining 44 patients were cigarette smokers during cetuximab-based anticancer therapy. Of the 44 smokers, 18 smoked more than 10 cigarettes per day. No statistically significant differences in terms of response rate (RR) and time to progression (TTP) were identified between previous smokers and never smokers. RR in actual smokers was 13.6% and was lower than RR reported for non-smokers (27.1%; p = 0.023). In addition, the median TTP was 5.5 months in the non-smokers versus 2.8 months in the current smokers (p < 0.0001). A difference in terms of overall survival (OS) was detected between the two groups (p = 0.03). Comparing smokers of more than 10 cigarettes per day and smokers of less than 10 cigarettes per day no differences were detected in RR, TTP or OS. Conclusions: Our results suggest that cigarette smoking during anticancer treatment with a cetuximab-based regimen may be responsible for a decrease in RR and lead to a lower TTP.     

Pulmonary clearance of [99mTc]DTPA and [99mTc]albumin in smokers

We measured the pulmonary clearance of [^99mTc]DTPA and [^99mTc]albumin for 3 h in 10 non-smokers and 10 healthy smokers. Seven of the non-smokers had a monoexponential clearance of [^99mTc]DTPA with a mean half-life of 66±18 min. The other three had a biexponential clearance of [^99mTc]DTPA with a fraction of radioactivity clearing rapidly (f_F) of 14±4%. Eight smokers had biexponential clearance of [^99mTc]DTPA. The half-life of the fast and slow clearance components was 1265 and 62611 min respectively. The f_F was 56±25%. Two of the smokers showed a monoexponential clearance of [^99mTc]DTPA with a half-life of 72 and 55 min. All non-smokers had monoexponential clearance curves for [^99mTc]albumin, compared with seven smokers. The half-life was 279±43 min in non-smokers and 236±64 min in smokers. The difference in half-life was not significant. In three smokers, the clearance curves of [^99mTc]albumin were significantly better described by a bi-exponential equation. The f_F was 22±9%. The effects of smoking on the clearance of [^99mTc]albumin appear to be qualitatively similar to those on the clearance of [^99mTc]DTPA. Clearance of [^99mTc]albumin seems less sensitive to the effects of smoking than clearance of [^99mTc]DTPA.     

Smoker identity among social smokers: theory-based approaches for anti-smoking interventions

Abstract

A large number of college smokers refuse to self-identify as smokers, instead referring to themselves as social smokers. With little or no information on how social smokers perceive risks and levels of efficacy related to smoking cessation, designing effective anti-smoking campaigns may be problematic. Based on the theoretical underpinning of the Risk Perception Attitude Framework, we investigated the impact of perceived risks and self-efficacy on the intention to quit smoking among social smokers and compared the findings to those who self-identify as smokers (i.e. admitters) and non-smokers (i.e. deniers). An online survey was conducted targeting college students who had smoked in the past 30 days. Of the 414 total participants, 111 self-identified as social smokers. Results show that deniers were no more willing to quit than admitters albeit with a greater self-efficacy. Deniers also tended to underestimate the risks of smoking and possessed greater feelings of self-efficacy. Admitters, in contrast, were higher in perceived risk but lower in self-efficacy. In addition, the cognitive paths to quit smoking via perceived risks and assessment of self-efficacy were compared between deniers and admitters. The importance of considering smoking identity is discussed and practical implications for anti-smoking campaigns are provided.     

The influence of smoking on semen quality, seminal microelements and Ca2+-ATPase activity among infertile and fertile men

ObjectiveTobacco smoking is now increasing rapidly throughout the developing world and is one of the biggest threats to current and future world health. Several studies have addressed the role of cigarette smoking on semen quality, but the exact mechanisms remain inconclusive. In order to evaluate the detrimental effects of smoking on semen quality among Saudi subjects, the levels of different seminal parameters in smokers were compared to non-smokers.Patients and methodsA total of 159 semen samples (61 smokers and 98 non-smokers) from men attending an infertility clinic for routine infertility workup were sub-grouped into fertile or infertile and were compared based on standard semen analysis (according to WHO guidelines), content of metals (magnesium, zinc and cadmium) and plasma membrane Ca²⁺-ATPase activity of sperms.ResultsCadmium concentration was found significantly higher in smokers than in non-smokers either in fertile or infertile group (2.9 ± 0.4 vs 1.4 ± 0.7; 2.9 ± 0.5 vs 1.3 ± 0.7 μg L^? 1; respectively). Together with this increase in seminal Cd a significant decrease in Ca²⁺-ATPase activity (21.5 ± 2.8 vs 33.71 ± 1.2; 20.7 ± 1.5 vs 35.07 ± 2.9 mmol min^? 1 mg^? 1 protein, p < 0.05), decrease in seminal zinc (109.8 ± 8.1 vs 189.7 ± 9.9 mg L^? 1, p < 0.01) and decrease in sperm motility (41.9% ± 2.9 vs 46.01% ± 2.5; 9.8% ± 2.4 vs 15.3% ± 2.7, p < 0.05) were found.ConclusionOur data demonstrate that cigarette smoking affects both Ca²⁺-ATPase activity and motility of the spermatozoa. These effects may be attributed to increased seminal cadmium and reduced zinc concentrations.     

Increased urinary excretion of a major thromboxane metabolite in early alcohol withdrawal

Summary. Urinary excretion of 2, 3-dinor-thromboxane B2 as a marker of in vivo thromboxane A2 (TXA2) biosynthesis was measured in six alcoholics 1 and 14 days after the cessation of heavy drinking using gas chromatography/mass spectrometry. Six non-alcoholic healthy volunteers served as controls. One day after alcohol withdrawal the excretion of the dinor metabolite was significantly higher (P<0–01) in the alcoholics (408 ± 42 pg mg^-1 creatinine) than in the controls (180 ± 30 pg mg^-1 creatinine) and was accompanied by a significantly reduced platelet count (103–0 ± 20–2×110⁹ 1^-1 vs. 194–0 ± 13–9×10⁹ 1^-1 in controls; P<001). The metabolite excretion fell then significantly (P<0–05) to 245 ± 53 pg mg^-1 creatinine 14 days after alcohol withdrawal and this was paralleled by an increase in platelet count to 453–5 ± 72–0×10⁹ 1^-1 (P<0–05). The present results support the hypothesis that TX-A₂ biosynthesis is increased in early alcohol withdrawal and strongly suggest platelets as a cellular origin of the increased TXA₂ formation.