Cigarette smoking and platelet function

To assess the influence of cigarette smoking on platelet activation, we studied the changes in intraplatelet and platelet-released serotonin (5-HT) and plasma levels and platelet-associated production of thromboxane B2 (TXB2), in 6 non smokers and 6 habitual smokers, before and after acute exposure to smoke.Before smoking, habitual smokers showed slightly higher, albeit not significantly, 5-HT platelet concentrations and TXB2 plasma levels, as well as lower TXB2 platelet production after collagen and even more after ADP stimulation (0.59±0.27 vs 1.35±0.46 and 0.99+0.47 vs 2.08±0.51 ng/108 platelets for habitual smokers vs controls, 4 and 10 min after ADP, p<0.02). No significant differences in platelet 5-HT release were observed.Acute smoking did not induce any significant change from baseline in either 5-HT or TXB2 for controls, while significantly reduced TXB2 production from ADP-challenged platelets from habitual smokers (0.30±0.15 vs 0.59±0.27 ng/108 platelets, immediately after smoking vs baseline, p<0.01). Ninety min after the completion of the smoking, the values had returned to baseline.Immediately after smoking, significant differences were found between habitual smokers and controls for TXB2 platelet production (2.76±1.78 vs 6.42±1.60, p<0.025 and 3.01±1.90 vs 6.44±2.26 ng/108 platelets, p<0.05, for habitual smokers vs controls, 4 and 10 min after the addition of collagen; 0.30±0.15 vs 1.20±0.84 and 0.79±0.50 vs 1.70±0.74 ng/10 8 platelets, p <0.05, after ADP stimulation). Differences were no longer significant 90 min after smoking. Our data indicate that cigarette smoking is associated with platelet dysfunction, which seems due to impairment of metabolic platelet capacity rather than increased platelet activation in vivo.     

Effect of cigarette smoking upon in vivo platelet function in man

In vivo platelet aggregation, measured by the Filtragometer procedure in the presence of all formed elements of the blood, is significantly increased after cigarette smoking. This effect appears to be independent of the nicotine concentration of the cigarette. The absorbed carbon monoxide content of the smoke, as noted by increased carboxy-hemoglobin, appears to be related to the alterations in platelet function that were noted, and may be an extremely important factor in mediating cigarette smoking's noxious effects.     

吸烟对男性住院精神分裂症患者认知功能的影响

目的：探讨吸烟对男性住院精神分裂症患者认知功能的影响。方法采用横断面研究,用精神分裂症认知功能成套测验共识版（M CCB ）对149例吸烟与75例非吸烟男性住院精神分裂症患者进行认知功能评估,同时用PANSS评估两组患者的临床症状。比较两组患者认知功能和临床症状的差异,并分析吸烟与认知功能的相关性。结果吸烟组和非吸烟组患者临床症状的差异无统计学意义。吸烟组M CCB中数字序列[（14．52±5．51）分比（17．39±5．54）分]、言语记忆[（17．11±5．56）分比（19．69±6．05）分]、视觉记忆[（13．41±8．10）分比（16．96±8．06）分]3个分测验得分均低于非吸烟组,差异具有统计学意义（P＜0．05）。吸烟组中,吸烟时间、吸烟量、吸烟指数与认知功能均无相关性（P＞0．05）。结论吸烟可能损害男性精神分裂症患者的认知功能,尤其是记忆力。     

Effects of Hydergine on platelet deposition on "active" human carotid artery lesions and platelet function

Effects of co-dergocrine mesylate (Hydergine), a drug widely used for the therapy of cerebral vascular disease on local platelet accumulation in the carotid artery region was studied by means of the platelet uptake ratio (PUR) and on the systemic platelet-vascular wall interaction as calculated from platelet half-life were investigated. A placebo controlled, double blind, randomised protocol was used, 18 patients were treated with co-dergocrine and compared to placebo (n = 18). Co-dergocrine treatment resulted in a significant decrease in platelet deposition, PUR decreased from 1.28 +/- 0.05 before treatment to 1.25 +/- 0.06 on day 5 of therapy with a statistically significant (p less than 0.001) in the paired comparison. In the control group the corresponding changes from 1.29 +/- 0.04 before to 1.28 +/- 0.04 did not show a p-value of less than 0.05 in paired comparison. Platelet half-life (72 +/- 11 before vs. 76 +/- 11 hours after 5 days of co-dergocrine treatment) showed a statistically significant (p less than 0.001) prolongation, whereas in the placebo group no relevant change of T/2 was observed (71 +/- 10 before vs. 72 +/- 10 hours on day 5, p greater than 0.10). No relevant effects on ADP-induced platelet aggregation, platelet-release reaction, platelet aggregate ratio, TXB2 plasma levels and thrombin-induced MDA-formation could be detected. These results indicate that co-dergocrine decreased in-vivo platelet residence time to atherosclerotic lesions of the carotid artery. Co-dergocrine may thereby be of benefit in prevention of mural thrombus formation and prevention of transient ischemic attacks, but also of atherosclerosis in man.     

Effects of fish oil supplementation on platelet survival and ex vivo platelet function in hypercholesterolemic patients

Little is known about the effects of dietary supplementation on platelet survival with low doses of n-3 and n-6 fatty acids in patients with hypercholesterolemia. The effects of a 6-week intervention with fish oil capsules (daily intake: 216 mg eicosapentaenoic acid, 140 mg docosahexaenoic acid, 390 mg gamma-linolenic acid, and 3480 mg linoleic acid) on in vivo platelet survival (111 In-oxine labeled platelets) and on ex vivo markers of platelet activation were investigated in a placebo-controlled, double-blind study with 26 hypercholesterolemic patients. In vivo platelet survival increased in the fish oil group (T) from a mean of 159+/-14 hours to a mean of 164+/-12 hours (p=0.025), whereas it remained unchanged in the placebo (P) group (T vs. P; p=0.055). Ex vivo, thromboxane B2 decreased from a mean of 225+/-16 to 212+/-21 ng/mL (p=0.003) in T but did not change in P (T vs. P: p=0.002). Malondialdehyde formation was lowered significantly by fish oil supplementation from a mean of 5.49+/-1.3 to 5.12+/-1.05 nM/10(9) platelets, p=0.005, as compared with P (T vs. P; p=0.018). The trendwise decrease in 11-DH-thromboxane B2 plasma levels was not significant nor was the increase in platelet sensitivity to prostaglandin I2 by fish oil. Baseline platelet survival in patients with hyperlipoproteinemia type IIa was not different from those with hyperlipoproteinemia IIb and response to treatment in terms of platelet activation markers was not either. The changes in platelet activation parameters in T were associated with significant reductions in cholesterol (-2.9%), low density lipoprotein cholesterol (-3.5%), and triglycerides (-12.4%). Both ex vivo and in vivo platelet activation parameters exhibited signs of decreased activation by a 6-week diet supplemented with n-3 and n-6 fatty acids, which might be beneficial in reducing atherothrombotic risk, in patients with hyperlipoproteinemia type IIa and IIb.     

The acute effect of smoking on platelet and endothelial release reaction is suppressed in chronic smokers.

Whilst increased plasma beta-thromboglobulin (beta TG), platelet factor 4 and thrombospondin levels are regarded as reflecting the release reaction of platelets, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels represent endothelial release reaction and/or damage. In this study including 12 smokers and 9 nonsmokers, we investigated the acute and chronic effect of smoking on these parameters and antithrombin III, protein S and fibrinogen, as well. Nonsmokers were found to have somewhat higher plasma levels of beta TG, t-PA and PAI-1 than chronic smokers, and 30 minutes after smoking two cigarettes, these levels and protein S levels of nonsmokers showed more prominent increases than of chronic smokers. It is speculated that chronic exposure to cigarette smoke may cause "exhaustion" or "receptor down-regulation" of platelets and endothelial cells, resulting with diminished release reaction of platelets and endothelium in response to acute smoking.     

Effects of calcium channel blockers on in vitro platelet function in whole blood using single platelet counting

The effects of various calcium channel blockers on in vitro platelet aggregation were studied using whole blood platelet counting. Diltiazem and verapamil inhibited aggregation caused by adrenaline 5 microM and collagen 2 micrograms/ml, but only at concentrations far in excess of those seen in clinical use. Nifedipine and nimodipine also inhibited aggregation to these agonists, but this seemed to be due to the solvent used. The solvent for these dihydropyridines contains 15% ethanol, 15% polyethylene glycol and 70% water, and the ethanol component is the most likely to have caused an antiaggregatory effect. Other studies showing an antiaggregatory effect of dihydropyridines may not have taken account of this solvent effect.     

Effects of varying dietary proteins on plasma lipids and rabbit platelet function

The aim of this paper was to study the effect of dietary proteins on rabbit platelet aggregation induced by ADP, collagen and thrombin. In addition, blood coagulation tests (Stypven, Stypven cephalin and cephalin kaolin plasma clotting times) were performed on these rabbits fed semi-synthetic diets containing animal protein (casein) or vegetable proteins (walnut or soybean). As part of this study, total cholesterol, HDL cholesterol, phospholipid and triglyceride plasma levels were determined and platelet fatty acid composition was analysed. The results show that the addition of walnut meal in the diet decreases platelet aggregability and total plasma cholesterol. The relative effects of casein, soybean and walnut protein on platelet aggregability best correlated with the ratio of lysine to arginine in the protein and the ratio of HDL to LDL. An increase in the ratio C20:5 n-3/C20:4 n-6 in platelet fatty acids was also seen in walnut and soybean protein-fed animals, but the changes were greatest in soybean protein-fed animals while inhibition of platelet aggregation was greatest in walnut protein-fed animals.     

Effects of some antibiotics on platelet function in vitro and in vivo

Very high concentrations of carbenicillin, bensylpenicillin, cephaloitin, cloxacillin and ampicillin, markedly impaired the platelet aggregation in human citrated plasma mediated by ADP, adrenalin, collagen and Thrombofax reagent. These concentrations of carbenicillin, bensylpenicillin and ampicillin also prolonged thrombin clotting time, possibly by interfering with the polymerization of fibrinogen to fibrin, Carbenicillin and bensylpenicillin exerted the same effect on platelets in citrated and in heparinized plasma from humans and in citrated plasma from dogs. The inhibitory effect was not bound to the platelets. Bleeding from standardized wounds in dogs defibrinogenated with Defibrase was increased after administration of carbenicillin and bensylpenicillin and these antibiotics also inhibited aggregation of platelets mediated by thrombin in plasma from such dogs. Lower concentrations of bensylpenicillin exerted only a moderate inhibition of platelet aggregation whereas moderate concentrations of carbenicillin, cephaloitin, cloxacillin, ampicillin, gentamycin, tetracyclin, lincomycin, erythromycin and sulfaisodimidin did not alter platelet aggregation or thrombin clotting time of human citrated plasma.     

Cigarette-smoking effect on platelet function

The immediate effect of cigarette-smoking on ADP-induced platelet aggregation and on platelet adhesiveness was investigated in 12 normal subjects aged 20 to 40, in 10 normal subjects aged 43 to 72 and in 10 patients with cerebrovascular disease aged 45 to 75. All the subjects were heavy smokers (more than 20 cigarettes a day). After smoking 2 cigarettes a significant increase in ADP aggregation and platelet adhesiveness was found in the group of young heavy smokers, while in the old subjects with or without cerebrovascular disease the increase in platelet activity was never significant. These data were discussed and some hypotheses for this higher reactivity of platelets from young people were suggested.     

Effects of etofibrate on platelet function: In vitro studies in human plasma

In vitro activity of Etofibrate (2-p-chloro-phenoxyisobutyrate-ethyl-2-hydroxynicotinate) on human platelet function was investigated in comparison with that of Clofibrate and nicotinic acid. Effects of this drug on platelet release reaction factor 3 availability, malondialdehyde production and prostacyclin-like activity synthesis were studied.Platelet release reaction was reduced by both Clofibrate and Etofibrate, but Etofibrate inhibition was twice that of Clofibrate. Etofibrate and nicotinic acid, on the other hand, achieved an stronger inhibition than Clofibrate in platelet malondialdehyde synthesis. Platelet factor 3 activity was reduced by Clofibrate and Etofibrate but not by nicotinic acid.No inhibitory activity on PGI₂-like activity in rat arterial wall was exhibited.Differences observed among these drugs are discussed in relation with their possible modes of action.     

Effects of smoking during antipsychotic withdrawal in patients with chronic schizophrenia

A number of studies have shown that patients with schizophrenia smoke more than other psychiatric patients and more than the general population. Also, medicated schizophrenics who smoke present more positive symptoms of schizophrenia than non-smokers. The objective of the present study was to assess the effect of smoking on ratings of psychopathology for 30 days following discontinuation of antipsychotic medication. The subjects were 101 treatment-resistant patients with schizophrenia who had been admitted to the inpatient service of Neuroscience Research Hospital (NRH), National Institute of Mental Health, between 1982 and 1994 to undergo studies involving discontinuation of antipsychotic medication. Patients were rated independently on a daily basis on the 22-item Psychiatric Symptom Assessment Scale (PSAS), an extended version of the Brief Psychiatric Rating Scale (BPRS). At baseline, ratings for Verbal Positive, Paranoia and Loss of Function were higher in smokers (n=65) than non-smokers (n=36), but a statistically significant difference was observed only for the Verbal Positive cluster. Analysis by gender revealed that male non-smokers had the lowest psychopathology ratings at baseline. There were no differences in Anxiety/depression, Behavior Positive, Deficit Symptoms or Mannerisms (a measure for abnormal involuntary movements). Following medication discontinuation, repeated-measure analysis demonstrated a 'time' effect for all the variables studied and a 'group' (smokers vs. non-smokers) effect for Verbal Positive, Paranoia, and Loss of Function. Post-hoc comparisons at individual time points showed significantly higher ratings for smokers at week 1 for Paranoia. No differences were observed at later time points. In conclusion, at baseline, smokers had more positive symptoms and were apparently more functionally impaired than non-smokers. This difference was no longer evident after a 30 day medication discontinuation period.     

Impaired platelet function among platelet donors

BACKGROUND: Platelet transfusions are effective for the prevention and treatment of bleeding in patients with disorders of platelet number and/or function. In recent years plateletpheresis concentrates have outnumbered pooled platelet concentrates, albeit with significant differences between nations. Thus, the platelet quality of individual donors has become increasingly important. The aim of this study was to gain an estimate for the prevalence of impaired platelet function among platelet donors. STUDY DESIGN AND METHODS: We determined the inter-donor variability in platelet plug formation with a PFA-100 analyzer, the prevalence of impaired thromboxane formation, and effects of the density in alpha2 integrin polymorphism and density. RESULTS: (i) Collagen-epinephrine induced closure time (CEPI-CT) showed a great inter-subject variability in platelet donors and was higher than in healthy controls (p = 0.008). One-fifth of donors had abnormal CEPI-CT values and 11% exceeded >300 s (max measurable value). (ii) Decreased serum thromboxane B2 levels were found in 9% of all donors, compatible with surreptitious intake of cyclooxygenase inhibitors or with an aspirin-like defect. CEPI-CT correlated inversely with TxB2-levels in donors and controls. (iii) The density of the alpha2-integrin correlated negatively with CEPI-CT and CADP-CT values in controls, but was not responsible for the observed impaired platelet function in donors. (iv) Finally, the ABO blood group system modulates closure times. CONCLUSION: In sum, a large number of platelet donors present with prolonged closure times. Decreased thromboxane formation and frequent platelet donation partly account for this observation.     

Effects of cigarette smoking on reward responsivity and cognitive function in brain injured individuals

Abstinence from smoking has been associated with acute impairments of performance in a number of tasks associated with incentive motivation and executive functioning in non-injured participants. The current study aimed to investigate the effects of smoking on various cognitive and motivational measures in 18 brain injured smokers, thus generalising previous findings from non-injured participants. A within-subjects cross-over design was utilised, to compare performance after an acute period of abstinence from smoking with performance after smoking. The test battery included measures of reward responsivity (a card-sorting task providing a behavioural index of incentive motivation), verbal fluency, and working memory. Reward responsivity was enhanced after a cigarette had been smoked compared to when abstinent. Performance on the card sorting task was particularly enhanced when the task was novel. There was no significant enhancement on any other measure. It was concluded that smoking has a direct effect on responsiveness to incentive, which we have found elsewhere to be closely related to motivation in therapy. Implications for clinical neuropsychological assessment and treatment are discussed.