Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion.

Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the alpha2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against alphaIIbbeta3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase alphaIIbbeta3-mediated platelet adhesion to albumin, dependent on alpha2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent.     

Tacrine restores cholinergic nicotinic receptors and glucose metabolism in alzheimer patients as visualized by positron emission tomography

Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [¹⁸F]-fluoro-deoxy-glucose (¹⁸F-FDG) (tracer for glucose metabolism); ¹¹C-butanol (cerebral blood flow) and (S)(−)- and (R)(+)-[N-¹¹C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of ¹¹C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(−)- and (R)(+)¹¹C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(−)¹¹C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement.     

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.     

In safe hands: a qualitative study on older adults’ experiences of a tailored primary health care unit

Objective: Today’s health care system faces challenges in meeting the needs of older people with multimorbidity. To better cope with these needs, tailored primary health care with geriatric competence and person-centred care has been suggested. The aim of this study was to explore older patients’ experiences of a tailored primary health care unit.Design: This was a qualitative study using semi-structured individual interviews and qualitative content analysis.Setting and patients: Nineteen patients were recruited from a tailored PHC unit for people aged 75 years or older in a region in central Sweden.Methods: The interview data were analysed using inductive category development.Results: In the analysis, the theme In safe hands when in need of primary health care emerged. The interviewees expressed a desire to participate in their own care. Easy access, enough consultation time and a calm environment, along with the PHC professionals’ welcoming and attentive approach enhanced their feeling of being in safe hands. PHC professionals were perceived as having geriatric knowledge and taking responsibility for the care of older patients. Although the interviewees experienced that they received attention for their health conditions, a need for a more preventive approach to care emerged.Conclusion: Older patients highly appreciated their tailored PHC unit and they emphasised that it was an improvement compared to the ordinary PHC centre. This study provides insights into older patients’ experiences, which may be helpful in the ongoing process of improving care for older patients in PHC.

KEY POINTS

• Older patients attending a tailored Primary health care (PHC) unit felt acknowledged, unlike in the ordinary PHC centre, which facilitated their participation in their care.
• The calm environment, specialist geriatric competence and ample patient contact time enabled them to feel secure and taken care of.
• Older patients expressed a need for an incorporation of social services and health promotion visits at the tailored PHC unit.

     

Salicornia dolichostachya organosolv fractionation: towards establishing a halophyte biorefinery

Halophytes are a potential source of lignocellulosic material for biorefinery, as they can be grown in areas unsuitable for the cultivation of crops aimed at food production. To enable the viable use of halophytes in biorefineries, the present study investigated how different organosolv process parameters affected the fractionation of green pressed fibers of Salicornia dolichostachya. We produced pretreated solids characterized by up to 51.3% ± 1.7% cellulose, a significant increase from 25.6% ± 1.3% in untreated fibers. A delignification yield of as high as 60.7%, and hemicellulose removal of as high as 86.1% were also achieved in the current study. The obtained cellulose could be completely converted to glucose via enzymatic hydrolysis within 24 h. The lignin fractions obtained were of high purity, with sugar contamination of only 1.22% w/w and ashes below 1% w/w in most samples. Finally, up to 29.1% ± 0.4% hemicellulose was recovered as a separate product, whose proportion of oligomers to total sugars was 69.9% ± 3.0%. To the best of our knowledge, this is the first report in which Salicornia fibers are shown to be a suitable feedstock for organosolv biomass fractionation. These results expand the portfolio of biomass sources for biorefinery applications.

An organosolv method was developed for the fractionation of fibers of a halophyte plant in a biorefinery approach. Salicornia dolichostachya was used as raw material allowing the production of cellulose, hemicellulose, and lignin fractions.     

Anticoagulant action of melagatran: a comparison between neonates and adults using calibrated automated thrombography (CAT)

In the present study, we comparatively evaluated the anticoagulant efficacy of the new direct thrombin inhibitor melagatran in cord vs. adult plasma. In contrast to heparin, melagatran does not require antithrombin as a cofactor. Thus, anticoagulant treatment with melagatran is of special interest in neonatal patients, whose plasma is relatively deficient in antithrombin. We evaluated the anticoagulant action of increasing amounts of melagatran (0.1–2.0 μmol/l) in both cord and adult plasma by means of calibrated automated thrombography (CAT) with respect to the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. Melagatran exhibited approximately the same ability to prolong lag times or TTPs in both cord and adult plasma. Similar concentrations (IC₅₀) of melagatran were required to double the lag times (0.44±0.04 μmol/l vs. 0.52±0.05 μmol/l) or to double the TTPs (0.91±0.08 μmol/l vs. 1.06±0.09 μmol/l) in cord vs. adult plasma. Melagatran exhibited a higher ability to suppress ETPs or thrombin peak heights in cord vs. adult plasma. Markedly lower concentrations (IC₅₀) of melagatran were required to suppress ETPs (0.27±0.03 μmol/l vs. 0.70±0.06 μmol/l) or thrombin peak heights by 50% (0.29±0.03 μmol/l vs. 0.53±0.04 μmol/l) in cord vs. adult plasma. We conclude that our results suggest a higher ability of melagatran to suppress thrombin formation in cord vs. adult plasma. Thus, lower amounts of melagatran might be required in neonates undergoing antithrombotic therapy.     

Provoked Vestibulodynia—Medical Factors and Comorbidity Associated with Treatment Outcome

IntroductionProvoked vestibulodynia (PVD) is the most common cause of dyspareunia in young women. The etiology is unclear, and there is little knowledge of how to predict treatment outcome.AimThe aim of this study was to identify medical factors associated with treatment outcome and coital pain in women with PVD.MethodsSeventy women previously treated for PVD at a vulvar open care unit completed questionnaires and a quantitative sensory testing session.Main Outcome MeasuresConcomitant bodily pain and treatment outcome were surveyed using a study specific questionnaire. Coital pain was rated on a visual analog scale (VAS), range 0–100. Psychometric screening was carried out using the Hospital Anxiety and Depression Scale. Pressure pain thresholds on the arm, leg, and in the vestibulum were measured using pressure algometers.ResultsMajor improvement/complete recovery was more likely in PVD patients with a maximum of one other concomitant pain disorder compared with patients with four or more (odds ratio = 7.8, confidence interval: 1.2–49.4, P = 0.03). In a multiple linear regression model, the number of other pain disorders (P < 0.01) and a diagnosis of primary PVD (P = 0.04) were positively associated with the coital VAS pain score. Women with secondary PVD reported major improvement/complete recovery to a higher extent than women with primary PVD (z = 2.11, P = 0.04).ConclusionA successful treatment outcome was more likely in PVD patients with fewer other concomitant pain conditions. The number of other bodily pain conditions was also associated to the intensity of the coital pain. Additionally, the results indicate higher incomplete response rates to treatment in women with primary PVD compared with secondary PVD. Heddini U, Bohm‐Starke N, Nilsson KW, and Johannesson U. Provoked vestibulodynia—Medical factors and comorbidity associated with treatment outcome. J Sex Med 2012;9:1400–1406.