Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Increase of microsomal glucose-6-phosphatase activity after chronic ethanol administration

To study the effect of chronic ethanol administration on the activity of hepatic microsomal glucose-6-phosphatase, female rats were pair-fed liquid diets with 36% of total calories either as ethanol or isocaloric carbohydrate (controls). The remainder of the diet contained 35% of total calories as fat, 18% as protein, and 11% as additional carbohydrate. Six weeks of ethanol feeding as isocaloric substitution for carbohydrate increased significantly the activity of glucose-6-phosphatase (expressed per mg microsomal protein) both in fed (38%; p < 0.001) and fasted 18%; p < 0.02) rats. When expressed per unit of body weight, the enzyme activity was increased even further both in fed (66%; p < 0.01) and fasted (43%; p < 0.01) rats. Another group of rats received diets containing 36% of calories either as ethanol or isocaloric fat. The remainder of the diet contained 11% of total calories as carbohydrate, 18% as protein, and 35% as additional fat. Six weeks of this ethanol feeding as isocaloric substitution for fat again increased glucose-6-phosphatase activity significantly. Ultracentrifugation in a Cs⁺-containing sucrose gradient to separate rough and smooth microsomes revealed that the increase in glucose-6-phosphatase activity after ethanol feeding occurred mainly in the smooth microsomal membranes.     

A national interactive web-based physical activity intervention in women, evaluation of the american heart association choose to move program 2006-2007

Increased physical activity (PA) is associated with improvement of cardiac risk factors and prevention of cardiovascular disease, yet many women remain sedentary. With rising Internet use, Web-based interventions provide an alternative to improve PA, but their effectiveness for change in PA and quality of life (QOL) in a real-world setting is unknown. Participants were United States women ≥18 years old who received 12 weekly PA modules and completed surveys on PA, QOL, and readiness for PA at registration (registration cohort, n = 3,796) or registration and 12 weeks (evaluation cohort, n = 892). QOL was assessed with a modified Short Form-36 with subscores for energy and well-being. Participants showed significant (p <0.001) favorable changes in PA (baseline, median 240 kcal/week, interquartile range 62 to 667; 12 weeks, 343 kcal/week, 131 to 828), stage of readiness for PA, and body mass index (baseline, 29.3 kg/m(2), 24.9 to 34.7; 12 weeks, 28.9 kg/m(2), 24.6 to 34.2). Significant improvements (p <0.0001) were also found in composite scores for energy and well-being. Compliance with PA guideline recommendations increased from 15.8% to 21.4%. Program weeks completed (p = 0.03), energy (p = 0.04), and well-being (p = 0.002) were significantly associated with achieving guideline compliance. In women reporting no PA at baseline (n = 88), program participation resulted in 54.6% achieving some PA and another 9.1% achieving total compliance with recommendations. In conclusion, in this national cohort of women, a 12-week Web-based intervention improved PA and QOL measurements, resulting in higher short-term PA guideline compliance and better QOL. Increasing use of this simple Web-based tool could improve PA and promote disease prevention.     

Sexual risk behaviors and acceptability of HIV pre-exposure prophylaxis among HIV-negative gay and bisexual men in serodiscordant relationships: a mixed methods study

The objective of this mixed methods study was to examine current sexual risk behaviors, acceptability and potential adoption of pre-exposure prophylaxis (PrEP) for HIV prevention, and sexual behavior intentions with PrEP adoption among HIV-negative gay and bisexual men (GBM) in HIV serodiscordant relationships. A multiracial/ethnic sample of 25 HIV-negative GBM in serodiscordant relationships completed a qualitative interview and a brief interviewer-administered survey. A modified grounded theory approach was used to identify key themes relating to acceptability and future adoption of PrEP. Participants reported engaging in sexual risk behaviors that place them at risk for HIV infection. Participants also reported a high level of acceptability for PrEP and willingness to adopt PrEP for HIV prevention. Qualitative themes explaining future PrEP adoption included: (1) the opportunity to engage in sex using a noncondom HIV prevention method, (2) protection from HIV infection, and (3) less anxiety when engaging in sex with an HIV-positive partner. Associated with the future adoption of PrEP, a majority (64%) of participants indicated the likelihood for an increase in sexual risk behaviors and a majority (60%) of participants also indicated the likelihood for a decrease or abandonment of condom use, both of which are in contrast to the findings from the large iPrEx study. These findings suggest that the use of PrEP by HIV-negative GBM in serodiscordant relationships carries with it the potential for risk compensation. The findings suggest that PrEP only be offered as part of a comprehensive HIV prevention strategy that includes ongoing risk reduction counseling in the delivery of PrEP to help moderate risk compensation.     

I. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in alcoholic liver disease: effects on drinking behavior by nurse/physician teams

BACKGROUND: This multicenter prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the effectiveness of polyenylphosphatidylcholine against the progression of liver fibrosis toward cirrhosis in alcoholics. Seven hundred eighty-nine alcoholics with an average intake of 16 drinks per day were enrolled. To control excessive drinking, patients were referred to a standard 12-step-based alcoholism treatment program, but most patients refused to attend. Accordingly, study follow-up procedures incorporated the essential features of the brief-intervention approach. An overall substantial and sustained reduction in drinking was observed. Hepatic histological and other findings are described in a companion article. METHODS: Patients were randomized to receive daily three tablets of either polyenylphosphatidylcholine or placebo. Monthly follow-up visits included an extensive session with a medical nurse along with brief visits with a study physician (hepatologist or gastroenterologist). A detailed physical examination occurred every 6 months. In addition, telephone consultations with the nurse were readily available. All patients had a liver biopsy before entry; a repeat biopsy was scheduled at 24 and 48 months. RESULTS: There was a striking decrease in average daily alcohol intake to approximately 2.5 drinks per day. This was sustained over the course of the trial, lasting from 2 to 6 years. The effect was similar both in early dropouts and long-term patients, i.e., those with a 24-month biopsy or beyond. CONCLUSIONS: In a treatment trial of alcoholic liver fibrosis, a striking reduction in alcohol consumption from 16 to 2.5 daily drinks was achieved with a brief-intervention approach, which consisted of a relative economy of therapeutic efforts that relied mainly on treatment sessions with a medical nurse accompanied by shorter reinforcing visits with a physician. This approach deserves generalization to address the heavy drinking problems commonly encountered in primary care and medical specialty practices.     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

Are men treated better than women? Outcome of male versus female patients after CABG using bilateral internal thoracic arteries

BACKGROUND: Apart from smaller native coronary arteries a lower number of anastomoses and a lower ITA incidence have been suggested as being responsible for the increased mortality in female patients compared to males. The aim of this study was to clarify whether the outcome of females might be a consequence of a different regimen in anastomosis and ITA frequency. METHODS: We evaluated operative data and early outcome of 6906 patients with isolated CABG operated between 1/96 - 7/03 3064 out of 5381 males received bilateral ITA (BITA) vs. 750 of 1525 females. Single ITA (SITA) was performed in 2126 males and 704 females. RESULTS: Demographic and operative data: average age for male patients was 64.0 +/- 9.2 years, for females 68.5 +/- 8.6 years ( p < 0.05). The prevalence of diabetes mellitus was significantly higher in females (34.6 % vs. 27.4 %, p < 0.01). Body mass index (BMI, 26.6 vs. 27.4 mean), incidence of main stem stenosis (23.0 % vs. 23.5 %), ejection fraction < 40 % (7.8 % vs. 10.1 %), urgent or emergent operations (13.1 % vs. 11.3 %) and number of performed anastomoses (3.2 vs. 3.5 mean) showed no significant difference between males and females. Total ITA frequency did not differ (95.3 % vs. 96.5 %), but BITA frequency was significantly higher (56.9 % vs. 49.2 %, p < 0.01) in male patients. Overall 30-day mortality was 2.8 % for males vs. 4.1 % ( p < 0.05) for females. Cardiac-related mortality was significantly higher in female patients (2.6 % vs. 1.1 %, p < 0.01). Non-cardiac-related mortality did not differ significantly. Graft-related mortality for males and females revealed 2.7 % in the BITA, 3.3 % in the SITA group and 6.9 % for patients without ITAs and reached statistical significance ( p < 0.01) for SITA or BITA vs. the no-ITA group, but not for BITA vs. SITA grafting. Nevertheless cardiac-related mortality in male and female patients without an ITA graft was more than two-fold higher compared to these with single ITAs and more than three-fold higher compared to those with BITA grafting. CONCLUSIONS: Female gender, frequently associated with diabetes mellitus, presents a predictor for increased mortality in CABG. A discrimination of women with respect to a restriction of ITA grafting could be confirmed only for bilateral ITAs. The superior results of bilateral ITA grafts are independent of gender.