The influence of the polyphenols of cider on plasmin and plasminogen activators

Preliminary findings suggested that the inhibitory activity on fibrinolysis produced by most varieties of cider is due to their content of polyphenols. In particular, the inhibitory activity co-eluted with the brown coloration on gel filtration, was removed by adsorption with polyvinylpyrrolidine, and was greatly reduced in a type of cider with a low concentration of phenolic compounds. The individual polyphenols of apple juice and ciders were examined for their ability to inhibit tissue activator, urokinase and plasmin. Neither phloridzin nor chlorogenic acid had any inhibitory activity at concentrations of 500 micrograms/ml while epicatechin had only a slight inhibitory effect at this concentration. The procyanidin fractions were markedly inhibitory on urokinase-induced clot lysis, the amidolytic activity of plasmin and on the fibrinolytic activities of plasmin, urokinase and tissue activator on fibrin plates: inhibition was noted at concentrations as low as 0.25 micrograms/ml. The order of inhibition was polymer greater than oligomer greater than trimer greater than dimer.     

Irritable bowel syndrome, chronic pelvic inflammatory disease and endometriosis: a comparison of symptomatology

BACKGROUND AND OBJECTIVES: Both irritable bowel syndrome and some gynaecological diseases can give rise to lower abdominal pain, which may result in diagnostic confusion. Disorders such as endometriosis and chronic pelvic inflammatory disease can be diagnosed definitively only by laparoscopy, which is seldom undertaken in the gastroenterological setting. It was the aim of this study to compare the symptomatology of irritable bowel syndrome with that of laparoscopically confirmed chronic pelvic inflammatory disease and endometriosis. PATIENTS AND METHODS: A symptom questionnaire was administered to 50 women with irritable bowel syndrome and 51 gynaecological patients (30 patients with endometriosis, 21 patients with chronic pelvic inflammatory disease). As the symptoms of the two gynaecological conditions were so similar, the groups were combined for the purposes of comparison with irritable bowel syndrome. RESULTS: Patients with irritable bowel syndrome suffered significantly more upper abdominal pain, colicky pain and exacerbation of pain by food or stress. They also experienced more disturbance of bowel habit, distension and nausea. In contrast, the only gynaecological features that were more common in the gynaecological patients were intermenstrual bleeding, premenstrual exacerbation of pain and forniceal tenderness. CONCLUSION: The presence of gastrointestinal symptomatology, especially bowel dysfunction, in a woman with lower abdominal pain is suggestive of irritable bowel syndrome. However, the history may not be so helpful in detecting gynaecological disease.     

Seasonal changes in concentrations of plasma hormones in the male ring dove (Streptopelia risoria)

Seasonal changes in concentrations of plasma LH, prolactin, thyroxine (T4), GH and corticosterone were measured in captive male ring doves exposed to natural lighting at latitude 56 degrees N. Plasma LH levels decreased steeply in autumn when the daylength fell below about 12.5 h but increased in November as the birds became short-day refractory. In comparison with plasma LH concentrations in a group of short-day refractory birds exposed to 6 h light/day from the winter solstice, plasma LH levels in birds exposed to natural lighting increased further in spring after the natural daylength reached about 12.5 h. There were no seasonal changes in plasma prolactin concentrations and plasma T4 concentrations were at their highest during December, January and February, the coldest months of the year. The seasonal fall in plasma LH levels in September was associated with a transitory increase in plasma T4, a transitory decrease in plasma corticosterone and a sustained increase in plasma GH. It is suggested that in the ring dove, short-day refractoriness develops rapidly in November to allow the bird to breed when the opportunity arises, during the winter and early spring. The annual breeding cycle is synchronized by a short-day induced regression of the reproductive system in the autumn, the primary function of which may be to enable the birds to meet the energy requirements for the annual moult. The changes in plasma T4, corticosterone and especially of GH at this time of year are probably concerned with the control of moult or the associated changes in energy requirements.     

Homozygosity for a conserved Mhc class II DQ-DRB haplotype is associated with rapid disease progression in simian immunodeficiency virus-infected macaques: results from a prospective study

In human immunodeficiency virus type 1 (HIV-1)-infected individuals, disease progression varies considerably. This is also observed after experimental infection of macaques with simian immunodeficiency virus (SIV). Major histocompatibility complex (MHC) genes may influence disease progression in both species. Homozygosity for Mhc-Mamu (Macaca mulatta)-DQB1*0601 was previously identified to be associated with rapid disease progression in SIV-infected macaques. To validate the association of this genotype with disease progression, a prospective study was carried out. Six unrelated monkeys homozygous for Mamu-DQB1*0601 and DRB1*0309-DRB*W201 and 6 heterozygous monkeys were infected with SIVmac. Five of the homozygous and only 1 of the heterozygous monkeys died rapidly after infection, with manifestations of AIDS. These results were validated by a retrospective survival analysis of 71 SIV-infected monkeys. The identified DQ-DRB genotype is frequent among monkeys of different breeding colonies and allows a fairly reliable selection before infection of monkeys predisposed for rapid disease progression.     

Human vascular endothelial cells with extended life spans: in vitro cell response,protein expression,and angiogenesis

An in vitro angiogenesis system was designed for screening angiogenic agonists and antagonists. In order to obtain large quantities of cells and reproducibility, human endothelial cells with extended life spans were developed by retroviral transfection. The resulting cells grown in a serum-free medium containing endothelial cell growth supplement (ECGS) have a telomerase activity, extended life spans of at least 21 passages, and an endothelial cell phenotype (diI-acetylated-LDL upake, factor VIII-related antigen, VEGFR-1 and R-2, and tissue-type plasminogen activator (tPA)) that resembled that of unaltered primary endothelial cells. Exceptions were (i) a higher expression of tPA, and (ii) a non-significant growth response to FGF-2 or VEGF stimulation. Within three-dimensional fibrin gels, specific cell clones rapidly formed tubular structures in a more reproducible manner than those observed with low-passage primary cells. Tube formation by primary endothelial cells and those with extended life spans was dependent upon FGF-2 and ECGS, respectively. Both cell types produced FGF-2 and VEGF cytokines. Increasing doses of suramin significantly decreased the size of microvessels formed by both cell lines. These functional results indicate that a vascular matrix system containing human cells with extended life spans can be successfully utilized as an in vitro assay for antiangiogenic compounds.     

How to improve screening in first-degree relatives of patients with premature coronary heart disease.

BACKGROUND: Guidelines on the prevention of cardiovascular disease recommend screening in close relatives of patients with premature coronary heart disease (CHD). This family history puts them at increased risk for CHD, independent of other major risk factors, but screening for CHD risk factors in these relatives is not widely practiced in Europe. This demonstration project examined how to improve screening of close relatives of patients with premature CHD in daily practice. METHODS: A controlled study design was used. Four hospitals were compared in a pre-test as to the actual screening of relatives of patients with premature CHD. Then they were arranged in pairs and randomly assigned to the Usual care (U) or Intervention group (I). An information and health education program--involving patients, relatives and family doctors--was developed in I to improve screening by the family doctor. RESULTS: The pre-test confirmed that screening of relatives of patients with premature CHD is poorly practiced in the four regions; no significant differences between I and U were observed. The screening of relatives during the study period reached 63.9% in I compared to 25.4% in U. This difference between I and U was present in siblings and offspring. The cardiovascular risk profile of the relatives of I was not optimal and needed improvement. CONCLUSION: Screening of first-degree relatives of patients with premature CHD can be significantly improved through a health education program. This is the first and necessary step to improve the management of risk factors in these people, who are at increased risk for CHD.     

COMMUNITY ACTIVISTS’ COMPETENCE: THE CONTRIBUTING FACTORS

This study examined the contribution of the personal and social resources to community activists' competence. The research population included 163 activists who engage in volunteer activity in traditional communities. The findings revealed that the activists' gender, supervision by community‐organizers, sense of mastery, sense of belonging to the community, citizen participation, representation, and perceptions of leadership all contributed significantly to the activists' competence. A comprehensive analysis of the findings is presented, as well as practical recommendations for community organization. The recommendations highlight the importance of professional supervision for community activists, which aims to develop perceptions of community leadership, community belonging, citizen participation, and representation in order to enhance the success of community activity. Finally, the examination of personal and social resources that contribute to activists' competence can facilitate identification of potential community activists, in addition to shedding light on the content that professional supervisors should incorporate in their work with activists.     

Evaluation of Bactec Mycosis IC/F and Plus Aerobic/F Blood Culture Bottles for Detection of Candida in the Presence of Antifungal Agents

Clinical practice guidelines recommend performing follow-up cultures for patients with candidemia in order to determine the time when Candida is cleared from the bloodstream. Since this requires culturing blood samples from patients undergoing antifungal treatment, we evaluated two blood culture bottles (the Bactec Mycosis IC/F [MICF], specifically adapted to the growth of fungi, and the Bactec Plus Aerobic/F [PAF], containing resins to inactivate anti-infective agents) for their effectiveness in detecting Candida albicans and Candida glabrata when seeded in concentrations of 1 CFU/ml and 10 CFU/ml, respectively, together with human whole blood and various antifungal agents in therapeutic peak serum concentrations (C_max). Significant differences between the MICF and PAF vials for the detection of Candida spp. were found when inoculated with caspofungin (0/12 versus 8/12) (P < 0.001) or amphotericin B (3/12 versus 12/12) (P < 0.001). Inoculation of fluconazole or voriconazole did not influence the effectiveness of detection in the MICF and PAF bottles (P = 1.0). Neither the MICF nor the PAF bottles detected Candida spp. reliably when seeded together with anidulafungin (1/12 versus 1/12) (P = 1.0) or micafungin (0/12 versus 1/12) (P = 1.0). The times to positivity of both bottles were significantly prolonged when antifungal agents were added compared to those of controls without antimycotic drugs (P < 0.001). Overall, the results of this in vitro study indicate that the PAF bottles detected Candida spp. more reliably than the MICF bottles when supplemented with certain antifungal agents. Consequently, clinical studies should evaluate whether this holds true when blood cultures from patients undergoing antifungal treatment are performed.     

Neural modelling of the semantic predictability gain under challenging listening conditions

When speech intelligibility is reduced, listeners exploit constraints posed by semantic context to facilitate comprehension. The left angular gyrus (AG) has been argued to drive this semantic predictability gain. Taking a network perspective, we ask how the connectivity within language‐specific and domain‐general networks flexibly adapts to the predictability and intelligibility of speech. During continuous functional magnetic resonance imaging (fMRI), participants repeated sentences, which varied in semantic predictability of the final word and in acoustic intelligibility. At the neural level, highly predictable sentences led to stronger activation of left‐hemispheric semantic regions including subregions of the AG (PGa, PGp) and posterior middle temporal gyrus when speech became more intelligible. The behavioural predictability gain of single participants mapped onto the same regions but was complemented by increased activity in frontal and medial regions. Effective connectivity from PGa to PGp increased for more intelligible sentences. In contrast, inhibitory influence from pre‐supplementary motor area to left insula was strongest when predictability and intelligibility of sentences were either lowest or highest. This interactive effect was negatively correlated with the behavioural predictability gain. Together, these results suggest that successful comprehension in noisy listening conditions relies on an interplay of semantic regions and concurrent inhibition of cognitive control regions when semantic cues are available.     

Chronic Stress Prevents Cortico-Accumbens Cue Encoding and Alters Conditioned Approach

Chronic stress impairs the function of multiple brain regions and causes severe hedonic and motivational deficits. One brain region known to be susceptible to these effects is the PFC. Neurons in this region, specifically neuronal projections from the prelimbic region (PL) to the nucleus accumbens core (NAcC), have a significant role in promoting motivated approach. However, little is known about how activity in this pathway changes during associative learning to encode cues that promote approach. Less is known about how activity in this pathway may be altered by stress. In this study, an intersectional fiber photometry approach was used in male Sprague Dawley rats engaged in a Pavlovian autoshaping design to characterize the involvement of the PL-NAcC pathway in the typical acquisition of learned approach (directed at both the predictive cue and the goal), and its potential alteration by stress. Specifically, the hypothesis that neural activity in PL-NAcC would encode a Pavlovian approach cue and that prior exposure to chronic stress would disrupt both the nature of conditioned approach and the encoding of a cue that promotes approach was tested. Results of the study demonstrated that the rapid acquisition of conditioned approach was associated with cue-induced PL-NAcC activity. Prior stress both reduced cue-directed behavior and impaired the associated cortical activity. These findings demonstrate that prior stress diminishes the task-related activity of a brain pathway that regulates approach behavior. In addition, the results support the interpretation that stress disrupts reward processing by altering the incentive value of associated cues.SIGNIFICANCE STATEMENT Chronic stress causes hedonic and motivational deficits and disrupts the function of the PFC. A specific projection from the prelimbic region of the PFC to the nucleus accumbens core (PL-NAcC) promotes approach behavior and is a strong candidate for contributing to stress-induced disruptions in motivation. However, it is not known how activity in this pathway encodes cues that promote approach, and how this encoding may be altered by stress. Here we show that the rapid acquisition of conditioned approach is associated with cue-induced activity in the PL-NAcC pathway. Prior stress both reduces cue-directed behavior and impairs the associated cortical activity. These findings demonstrate that stress diminishes task-related activity in a brain pathway that regulates approach behavior.