Vitamin E reduces platelet adhesion to human endothelial cells in vitro

Although it has been reported that vitamin E (alpha-tocopherol) can reduce platelet adhesiveness and aggregation in vivo, the mechanism is still unknown. Therefore, the aim of the present study was to determine whether incubations of platelet-rich plasma (PRP) with vitamin E influence platelet adhesion to cultured endothelial cells. To exclude blood plasma involvement, also washed platelets were pretreated with alpha-tocopherol. Vitamin E (0.5-1.0 mM) was added to PRP or washed platelets. Endothelial cells in monolayer were incubated with thrombin-activated platelets (1 or 2 U/ml). After 1 hr of incubation, non-adhered platelets were removed and counted. Treating of PRP with alpha-tocopherol inhibited platelet adhesion to endothelial cell monolayer. This effect was dose dependent on concentrations of alpha-tocopherol and thrombin. In our experiments PRP was treated with alpha-tocopherol and endothelial cell monolayer was used as test surface. These findings agree with previous observations on the adhesivity of platelets to synthetic surfaces after dietary vitamin E in healthy volunteers. When washed platelets were incubated with alpha-tocopherol, no significant reduction of adhesion was detectable. As preincubation of washed platelets with alpha-tocopherol does not inhibit platelet adhesion, it may be supposed that the effect of vitamin E does not occur in a directly cellular mechanism. The data suggest that alpha-tocopherol may reduce platelet adhesiveness probably after incorporation by plasma lipoproteins.     

Functional bases for a central serotonergic involvement in classic migraine: a speculative view

The r?le of serotonin (5-HT) in the cerebrovascular bed is the subject of the following review. Cerebral blood vessels are supplied with 5-HT-containing fibres which originate in the raphé nuclei in the brainstem. The activation of this system may result in a constriction of large arteries and a dilatation of arterioles. Intra-arterial administration of 5-HT causes reduction in cerebral blood flow and metabolism provided it bypasses the blood-brain barrier. The findings, marked changes in plasma levels of 5-HT and in cerebral blood flow during a classic migraine attack, are suggestive of an involvement of the 5-HT system.     

Sex and the cystectomized male: A lack of communication,a need for education

When cancer of the bladder is treated by removal of the malignant organ, there is a high incidence of impotency in males. A retrospective study of 71 adult patients revealed misconceptions, misinformation, and misinterpretation that could have been alleviated by more timely and appropriate counsel. Nurse-enterostomal therapists are identified as potentially valuable sex counselors but their training in this field is limited. A need for patient education is demonstrated and a plea for follow-up attention to sexual concerns in the extended postoperative period is issued.     

Effects of gustatory stimulants of salivary secretion on salivary pH and flow: a randomized controlled trial

Objectives:  To compare salivary pH changes and stimulation efficacy of two different gustatory stimulants of salivary secretion (GSSS).
Setting:  Portuguese Dental Faculty Clinic.
Design:  Double blind randomized controlled trial.
Subjects:  One hundred and twenty volunteers were randomized to two intervention groups. Sample sized was calculated using an alpha error of 0.05 and a beta of 0.20.
Materials and methods:  Participants were randomly assigned to receive a new gustatory stimulant of secretory secretion containing a weaker malic acid, fluoride and xylitol or a traditionally citric acid-based one. Saliva collection was obtained by established methods at different times. The salivary pH of the samples was determined with a pH meter and a microelectrode.
Main outcome measures:  Salivary pH variations and counts of subjects with pH below 5.5 for over 1 min and stimulated salivary flow were the main outcome measures.
Results:  Both GSSS significantly stimulated salivary output without significant differences between the two groups. The new gustatory stimulant of salivary secretion presented a risk reduction of 80 ± 10.6% (95% CI) when compared with the traditional one.
Conclusions:  Gustatory stimulants of salivary secretion with fluoride, xylitol and lower acid content maintain similar salivary stimulation capacity while reducing significantly the dental erosion predictive potential.     

Nutritional and vitamin status in patients with neuroendocrine neoplasms

Symptoms of gastroenteropancreatic located neuroendocrine neoplasms(GEPNENs) are often related to food intake and manifest as abdominal pain or diarrhoea which can influence patients nutritional status. Malnutrition is common in cancer patients and influences quality of life, treatment options and survival but is also present in up to 40% of patients with GEP-NENs. As part of malnutrition there are often deficiencies in fat-soluble vitamins, mainly vitamin D. Little knowledge exists on trace elements. Several factors influence the development of malnutrition such as size and localisation of the primary tumour as well as metastases, side effects from treatment but also hormone production of the tumour itself. One of the main influencing factors leading to malnutrition is diarrhoea which leads to dehydration and electrolyte disturbances. Treatment of diarrhoea should be guided by its cause. Screening for malnutrition should be part of routine care in every GEP-NEN patient. Multidisciplinary treatment including dietician support is necessary for all malnourished patients with GEP-NENs.     

Redox-sensitive events in Fas-induced apoptosis in human NK cells include ceramide generation and protein tyrosine dephosphorylation

We previously reported that intracellular oxidation-reduction (redox) regulates NK cell functions and that IL-2-activated NK cells undergo apoptosis upon contact with NK-sensitive target cells. We now report that apoptosis in activated human NK cells is also regulated by redox. Thiol deprivation increased apoptosis in NK cells induced by anti-Fas mAb or Fas ligand-transfected cells, and pretreatment of cells with N- acetyl cysteine, which increased intracellular glutathione, partially inhibited the apoptosis and reversed the effect of thiol-deficient medium, suggesting that Fas-induced apoptosis in NK cells is also redox sensitive. Thiol deprivation did not alter cell surface Fas expression, but did increase ceramide generation following Fas engagement. Although exogenous ceramides induced apoptosis of NK cells, thiol depletion had no effect on this apoptosis. Thiol deprivation increased CPP32 activation induced by Fas engagement, but not by ceramides. These findings suggest that, if ceramide is required for Fas-induced apoptosis, thiol deprivation affects the Fas-mediated signaling pathway at the generation of ceramide and/or upstream thereof. Though tyrosine phosphorylation following Fas engagement was not significantly affected by thiol deprivation, tyrosine dephosphorylation was delayed, suggesting that tyrosine phosphatases may also be redox sensitive. The notion that dephosphorylation is important in the Fas signaling pathway is supported by the finding that tyrosine phosphatase inhibitors significantly enhanced both CPP32 activity and apoptosis following Fas ligation. We conclude that events downstream of tyrosine phosphorylation and upstream of CPP32 activation, including tyrosine dephosphorylation and possibly ceramide generation, are sensitive to regulation by redox in human NK cells, requiring a reducing environment for optimal protection from apoptosis induced by Fas ligation.