Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition

Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country-specific dietary questionnaires. After a mean follow-up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72–1.10; p-trend = 0.70). Furthermore, no evidence for effect-measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.     

ELISA for the detection of the lymphokine soluble immune response suppressor

Murine soluble immune response suppressor (SIRS) is a product of Ly 2+ suppressor T cells which is activated to SIRSox by peroxide produced by macrophages. SIRSox inhibits cell division by normal and transformed cell lines and antibody secretion by B lymphocytes. Rat monoclonal anti-SIRS antibodies were developed to determine if ELISA methodology could replace bioassays for quantitation of SIRS in biological samples. Purified SIRS, applied to nitrocellulose, was detected with an avidin-biotin-horseradish peroxidase system. This ELISA was capable of detecting pg quantities of SIRS and detected SIRS after fractionation by high performance liquid chromatography. However, SIRS in crude supernatant fluids was undetectable by this method, presumably due to the small percentage of SIRS protein in relation to total protein in these samples. Thus, a competitive ELISA was adopted which, in initial experiments, detected SIRS in impure sources. This competitive ELISA may be useful in evaluating the presence or absence of SIRS in various biological samples.     

Two different pathways of interferon mediated suppression of antibody secretion

Interferon suppresses a variety of in vitro immune responses by a mechanism which has not been well defined. Both direct suppression and activation of suppressor T cells have been suggested as possible mechanisms of interferon action. In an attempt to examine this question interferon-alpha (IFN alpha)-mediated suppression of a plaque forming cell response to a T cell independent antigen by spleen cells or by B cells was examined. Somewhat greater quantities of IFN alpha were required to suppress plaque forming cell responses by B cells than by spleen cells to the antigen fluoresceinated-Brucella abortus (FITC-BA). However, suppression of spleen cell responses could be blocked by addition of either 2-mercaptoethanol, levamisole or monoclonal antibodies against the lymphokine, soluble immune response suppressor (SIRS), whereas suppression of B cell responses by interferon-alpha was unaffected by these agents. Each of these agents interferes with SIRS mediated suppression of immune responses. Addition of T cells to B cell cultures stimulated with FITC-BA did not affect the total plaque forming cell response nor the extent of suppression by IFN alpha, but it did restore 2-mercaptoethanol sensitivity to IFN alpha-mediated suppression. As few as 1 X 10(5) T cells were effective and it was necessary to add T cells within 3 h of addition of IFN alpha to confer 2-mercaptoethanol sensitivity to IFN alpha mediated suppression. These data suggest that IFN alpha can suppress immune responses by two different pathways and that in the presence of T cells, activation of suppressor T cells is the dominant pathway. The presence of T cells must also prevent direct suppression of B cells by IFN alpha.     

Hormone replacement therapy reduces the reactivity of monocytes and platelets in whole blood — A beneficial effect on atherogenesis and thrombus formation?

OBJECTIVE: Our purpose was to investigate the effects of hormone replacement therapy on the reactivity of monocytes and platelets in whole blood, measured by tissue factor activity, tumor necrosis factor-α, and thromboxane B₂.STUDY DESIGN: Thirty-two women were randomized into either transdermal or oral combined hormone replacement therapy and underwent blood sampling before and after 3 and 12 months of treatment. The tissue factor activity in monocytes was measured both in unstimulated whole blood and after a weak lipopolysaccharide stimulation. Tumor necrosis factor-α and thromboxane B₂ formation in plasma were measured after a weak lipopolysaccharide stimulation of whole blood.RESULTS: After 12 months of hormone replacement therapy there were significant reductions of tissue factor activity in both unstimulated and lipopolysaccharide-stimulated monocytes (p < 0.001) and significant reductions in the formation of tumor necrosis factor-α (p < 0.03) and thromboxane B₂ (p < 0.02). There were no differences in these parameters between the transdermal and the oral groups. No changes were observed after 3 months of therapy.CONCLUSION: Twelve months of hormone replacement therapy reduces cellular activation of blood monocytes and platelets; these changes may account for some of the beneficial effects in reducing the risk of cardiovascular disease.     

Use of freshly prepared rat hepatocytes to study toxicity of blooms of the blue-green algae Microcystis aeruginosa and Oscillatoria agardhii

Extracts from blue-green algal blooms (Microcystis aeruginosa and Oscillatoria agardhii) from different lakes in southeastern Norway were tested for toxicity toward freshly prepared rat hepatocytes. The toxicity effects were scored by means of morphological studies of the cells and by measuring leakage of the enzyme lactate dehydrogenase (LDH) from the cells. The results with the hepatocytes correspond well with results from the traditional mouse bioassay, concerning both ability to distinguish between toxic and nontoxic samples and estimation of relative toxicity. Morphological changes due to toxic effects on the plasma membrane appeared earlier than leakage of enzyme from damaged cells. The results indicate that the hepatocyte-toxicity assay system might be well suited for screening purposes concerning water contamination by blue-green algae.     

An evaluation of the mouse bioassay applied to extracts of 'diarrhoetic' shellfish toxins.

The standard mouse bioassay, used to assess 'diarrhoetic shellfish poison' (DSP), is based on intraperitoneal administration of toxic mussel extracts, and monitoring of survival time within a 24-hr period. Toxic effects on mice were examined for extracts of mussel samples from two different regions of south Norway known to possess toxins of specific properties. Both samples revealed an exponential pattern in the dose-response relationship. Whereas the time lag from injection to death was linearly dependent on mouse weight, the effect of weight also increased with decreased sample toxicity. When tested with doses adjusted for weight, a marked individual variation was found within all size groups of mice. The results imply that, regarding prohibition limits for distribution and sale of mussels, a certain degree of variation with regard to time should be accepted in the testing of parallel samples. On the basis of the results, a revised method for the determination of toxicity by mouse bioassay is proposed for DSP testing. The method is based on administration to two mice of size-adjusted doses of extracts, followed by a 4-hr surveillance period and a 1-hr upper limit of acceptable time variation between parallel samples. The method shows advantages regarding savings of time and money, in precision in determination of toxicity level, as well as curtailed exposure to toxin and reduced suffering of laboratory animals.     

Homocysteine levels, haemostatic risk factors and restenosis after carotid thrombendarterectomy.

OBJECTIVES: To investigate the effect of elevated serum homocysteine and haemostatic as well as clinical risk factors on the tendency to restenosis after carotid artery thrombendarterectomy. DESIGN: A prospective, observational study. PATIENTS AND METHODS: In the period from October 1999 to October 2002, 86 patients were subjected to 96 carotid endarterectomies because of internal carotid artery stenoses. The carotid stenoses were symptomatic in 86 cases (90%). Fasting plasma homocysteine, fibrinogen, D-dimer and activated protein C resistance were measured the day before surgery. Follow-up was done 1, 3, 6, 12 and 18 months postoperatively and yearly thereafter with clinical assessment and triplex ultrasonography. The median follow-up time was 17 months (range 9-42 months). Freedom from restenosis was estimated with Kaplan-Meier curves, using log-rank test for comparison between groups. Variables found to be significantly related to restenosis rates were included in a multivariate analysis performed with the Cox proportional hazards model. Comparison of means of continuous data between two groups was done with Student's t-test and more than two groups with one-way analysis of variance. RESULTS: Restenoses within 12 months of the operation occurred in 11 cases (11%). Univariate analysis revealed that plasma homocysteine values < or =10 micromol/l and freedom from ischaemic heart disease were both significantly associated with an increased risk of restenosis (p=0.0076 and 0.0059). However, multivariate analysis showed that only plasma homocysteine values <10 micromol/l were independently and significantly associated with an increased risk of restenosis (p=0.046). There were no associations between the degree of atherosclerotic affection of the precerebral circulation or symptoms on one hand and the levels of homocysteine, fibrinogen, D-dimer and activated protein C resistance on the other. CONCLUSION: There seems to be an independent, significant association between homocysteine values within the lower two thirds of the normal range and restenosis after carotid endarterectomy. Studies on the biological properties of human endothelial cells from different types of vasculature and different locations, specifically with respect to homocysteine metabolism and its effect, are warranted.     

Contraction of knee flexors and extensors in skiing related to the backward fall mechanism of injury to the anterior cruciate ligament

The purpose of this study was to examine the motion pattern and muscle activity during jumping and landing in downhill skiing to estimate the muscular involvement during the jump-landing-backward fall-anterior cruciate ligament (ACL) injury. A digitized 2-D video motion analysis and a synchronous 8-channel electromyography registration was performed over a jump on a downhill slope during 3 runs by 2 skiers and during 6 control jumps in the laboratory. The knee flexors (lateral gastrocnemius and biceps femoris) were recruited before touchdown and mean 60 ms earlier than the extensors (vastus lateralis and rectus femoris). Extensors and flexors reached peak activity simultaneously at the instant of landing. The knee flexion angle at the instant of landing was mean 36°. As the landing was stabilized, the extensor activity persisted during eccentric work at increasing knee flexion as a corresponding flexor relaxation took place. The control jump in the laboratory showed a similar order of recruitment and timing of muscle contraction. The gastrocnemius was recruited mean 96 ms earlier and the biceps femoris mean 63 ms earlier than the extensors. This recruitment pattern during the landing movement suggest a learned motor program engaging the kinetic chain of the lower extremity to intercept the landing energy. The results also indicate that the knee flexor activity may protect the ACL at the instant of landing but that it is minimal shortly thereafter and probably not able to protect the ACL when a backward fall occurs. The knee was flexed substantially as the extensors became the dominating muscles. Thus, their ability to apply any anterior drawer force able to rupture the ACL is questioned.     

Postdiagnosis body fatness,recreational physical activity,dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m² in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.