Marital status and survival in cancer patients: A systematic review and meta-analysis.

BACKGROUND: In recent years, authors have repeatedly reported on the significance of social support in cancer survival. Although overall the studies appear to be convincing, little is known about which types of social support promote better survival rates, and which subgroups of cancer patients are more susceptible to the benefits of it. The aim of this study was to identify, organize, and examine studies reporting on the significance of social support in cancer survival. METHODS: The PubMed, CINAHL and EBSCO databases were searched using the keywords social support/marital status, cancer, and survival/mortality. Where possible we used a meta-analytical approach, specifically a random effect model, in order to combine the results of the hazard ratios in studies from which this information could be obtained. When interpreting clinical relevance, we used the number needed to treat (NNT). RESULTS: Better survival was observed in married patients when compared to unmarried (single, never-married, divorced/separated, and widowed) in overall and cancer-specific survival. Gender group differences showed that the association was statistically significant only in cancer-specific survival when comparing divorced/separated male and female cancer patients (p < 0.001), thus confirming results from the previous meta-analysis. CONCLUSIONS: Being unmarried is associated with significantly worse overall and cancer-specific survival. The most vulnerable group found in our study were divorced/separated men. The results of this review can motivate physicians, oncologists, and other healthcare professionals to be aware of the importance of patients' social support, especially in the identified sub-group.

Real-life dental examination elicits physiological responses different to visual and auditory dental-related stimuli.

BACKGROUND: Previous studies on dental anxiety have examined the psychophysiological responses evoked in dentally anxious subjects by dental-related stimuli, but not during a real-life dental examination, which was achieved in the present study. METHODS: The heart rate, skin conductance level, and heart rate variability of 25 subjects with dental anxiety and 25 healthy controls were examined. Anxiety was determined by the Modified Dental Anxiety Scale and the Dental Anxiety Scale-Revised. The psychophysiological reactions of the two groups were compared during exposure to dental-related pictures, dental-related sounds, and an actual examination in a dental surgery. RESULTS: All the dental-related stimuli provoked an increase in heart rate, i.e. visual stimuli (p<0.001; 95% CI 0.98-3.95 bpm), auditory stimuli (p<0.001; 95% CI 1.34-4.99 bpm), and a dental examination (p<0.001; 95% CI 1.26-5.39 bpm). Dental-related pictures provoked inferior skin conductance level changes compared to dental-related sounds and the dental examination (visual modality vs auditory p<0.001; 95% CI 0.039-0.152; visual modality vs examination p<0.001; 95% CI 0.083-0.275). Heart rate variability manifested in a complex pattern of responses to the dental examination. However, when exposed to all three dental-related stimuli presentation conditions, the heart rate (F = 0.352, p = 0.556), skin conductance level (F = 0.009, p = 0.926), and heart rate variability parameters of subjects with dental anxiety did not differ in comparison to the healthy controls. CONCLUSIONS: This pilot study represents an evaluation of psychophysiological reactions during a real-life dental examination compared to single modality stimuli, and shows that a real-life dental examination provokes an increase in heart rate, heart rate variability and skin conductance level. Additionally, autonomic responses did not differ between the experimental and control groups. The key issue for future studies is the effect of real-life situations on the physiological and psychological state of the subjects, which should be considered when planning new research and studied in depth.

Increased Risk-Taking Behaviour and Brain-Derived Neurotrophic Factor Val66Met Polymorphism Correlates to Decreased Serum Brain-Derived Neurotrophic Factor Level in Heroin Users.

BACKGROUND: This study has examined the relationships and interactions between serum brain-derived neurotrophic factor (BDNF) levels, BDNF Val66Met polymorphism and self-reported risk-taking behaviour in individuals with a history of heroin use undergoing outpatient treatment in comparison to healthy individuals. METHODS: We enrolled 167 heroin users and 86 healthy subjects and examined serum BDNF levels, Val66Met polymorphism, and personal characteristics using Connor Davidson Resilience Scale, Risk-taking (RT) propensity questionnaire, and Personality Assessment Inventory. RESULTS: Heroin users had significantly higher serum BDNF levels than controls. In addition, serum BDNF levels were significantly higher in Val/Val carriers than in Met/Val or Met/Met in all recruited subjects. Furthermore, a stepwise multiple regression analysis of serum BDNF levels as a dependent variable with related factors showed that in heroin users, Alcohol Use Disorder Identification Test score, anxiety and RT score were found as independent contributors to serum BDNF levels. When performing gene-environment interaction it was additionally found that heroin users with self-reported high risk-taking behaviour had significantly lower levels of serum BDNF among heroin users with the Met allele. CONCLUSIONS: These results indicate that genetic variant Met66 decreased the serum BDNF levels in combination with self-reported risk-taking propensity among heroin users. If results of future work confirm the influence of this combined effect between neurotrophic genotype and risk-taking behaviour, 66Met carriers might require higher levels of intervention to overcome their drug use pattern and risky behaviour.

Cardioprotective effects of silver fir (Abies alba) extract in ischemic-reperfused isolated rat hearts.

BACKGROUND: Silver fir trunk extract (SFTE) is a complex mixture of antioxidative polyphenols (lignans and phenolic acids) from the trunks of silver fir trees (Abies alba, lignum). In our previous study, we have shown that SFTE exerts strong antioxidative and protective effects against atherogenic, diet-induced arterial wall damage. OBJECTIVE: The aim of the present study was to test the potential protective effects of SFTE and its compounds, two phenolic acids (p-coumaric and protocatechuic acids) in ischemia-reperfusion injury of isolated rat hearts. DESIGN: Isolated hearts of Wistar rats aged 4-8 weeks were exposed to perfusion, ischemia, and reperfusion periods. The experiments were performed using the following five groups: control, SFTE (10 µg/L), SFTE (100 µg/L), protocatechuic acid, and p-coumaric. Aortas were isolated to measure vascular responses in the presence of Nω-Nitro-L-arginine. RESULTS: SFTE dose-dependently reduced ischemic-reperfusion heart damage, which was indicated as the decrease in the lactate dehydrogenase (LDH) release rate and arrhythmias duration by 80% and an increase in coronary flow rate during the reperfusion period. Two tested compounds (p-coumaric and protocatechuic acids) acted less cardioprotective, since they decreased the duration of arrhythmias only by 40 and 45%, respectively, and did not decrease LDH release rates during the reperfusion period. Only p-coumaric acid increased coronary flow rates, whereas protocatechuic acid did not. CONCLUSIONS: We conclude that the SFTE exerted the strongest cardioprotective effect, whereas its constituents (the p-coumaric and protocatechuic acids) were less effective in inducing cardioprotection.

The "Rise-Peak-Fall" Pattern of Time Dependency of the Cardiovascular Pleiotropic Effects of Treatment With Low-dose Atorvastatin, Losartan, and a Combination Thereof in Rats.

Treatment with low, subtherapeutic doses of statins and sartans expresses beneficial pleiotropic effects on the arterial wall. The present study explored whether these effects depend on treatment duration. Wistar rats were randomly divided into 4 groups and received low-dose atorvastatin, low-dose losartan, their combination, or saline (control) daily. After 4, 6, 8, and 10 weeks of treatment, the animals were anesthetized, blood samples taken, and hearts and thoracic aortas isolated. Thoracic aorta endothelium-dependent relaxation and parameters of the isolated heart exposed to ischemic-reperfusion injury were assessed along with blood serum parameters and vasoactive genes expression. Low-dose atorvastatin, losartan, and especially their combination showed the characteristic time dependency of all studied parameters (thoracic aorta relaxation, isolated heart parameters, C-reactive protein values, genes encoding endothelial nitric oxide synthase, and CD40). The peak in efficacy was observed after 6 weeks of treatment and subsequently steadily declined. The peak versus control values were significant for all measured parameters. Only a combination of atorvastatin and losartan increased nitric oxide and decreased asymmetric dimethylarginine. A characteristic time-dependent "rise-peak-fall" pattern of the cardiovascular pleiotropic effects of statins and sartans in subtherapeutic low doses was revealed. Evidently, resistance to the explored treatment occurs after a certain period.

Bone remodeling during orthodontic tooth movement in rats with type 2 diabetes.

INTRODUCTION: Type 2 diabetes is known to affect bone metabolism. In this study, we aimed to determine the effects of type 2 diabetes on bone remodeling during orthodontic tooth movement. METHODS: The 48 rats were divided into 4 groups: Wistar control group (n = 8), Goto-Kakizaki (GK) control group (n = 8), Wistar appliance group (n = 16), and GK appliance group (n = 16). The distances between the teeth were measured weekly. On day 42, maxillary alveolar bone specimens were obtained for histologic evaluation and determination of the gene expression levels of the receptor activator of nuclear factor Ò¡B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG). RESULTS: No significant difference was observed in the levels of tooth movement between the 2 appliance groups. After orthodontic force application, the alveolar bone volume and osteoblast surface in the GK rats were diminished compared with those in the Wistar rats. The increase in the osteoclast surface relative to the control groups was 2.4-fold greater in the GK rats than in the Wistar rats. Significant upregulations of the RANK and OPG gene expression levels in the Wistar appliance group were observed. The RANKL/OPG ratio was increased in the GK appliance group compared with the Wistar appliance group. CONCLUSIONS: Diminished bone formation and slightly increased bone resorption were observed during orthodontic tooth movement in the rats with type 2 diabetes.

Silver fir (Abies alba) trunk extract protects guinea pig arteries from impaired functional responses and morphology due to an atherogenic diet.

BACKGROUND: Diet, rich in plant polyphenols prevents atherogenesis that manifests as reduced vascular relaxation and formation of plaques. HYPOTHESIS: Atherosclerosis could be reduced by the intake of silver fir (Abies alba) extract (SFTE), rich in polyphenols. STUDY DESIGN: Chronic, in vivo treatment animal study. METHODS: Guinea pigs (Cavia porcellus) were fed for 8 weeks with one of the following three diets: atherogenic, basic or atherogenic + SFTE. After isolation, we measured the relaxation and contractile responses of the thoracic aorta. Additionally, we measured the area of fatty plaques on the aortic walls. RESULTS: Compared to the basic diet, the atherogenic diet decreased the ability of the aorta to relax by 63% (p < 0.001). The addition of SFTE to the atherogenic diet improved the aorta relaxation response compared to that of the atherogenic diet without SFTE (the decrease relative to the basic diet was 26%, p < 0.001). The aorta contractility did not differ between the groups. The SFTE group generated significantly fewer atherosclerotic plaques than did the atherogenic group. The areas of atherosclerotic plaques were 7.4, 0.3 and 1.6% in the aortas of guinea pigs receiving atherogenic, basic or atherogenic + SFTE diets, respectively. CONCLUSIONS: In a guinea pig model, prolonged treatment with antioxidative polyphenol-rich SFTE prevents aortic functional and morphological changes caused by an atherogenic diet.

The role of gender and sex hormones in ischemic-reperfusion injury in isolated rat hearts.

To establish potential anti-ischemic effects of testosterone and estradiol on myocardium we used isolated rat hearts in accordance with Langendorff, exposed to 40 min of ischemia and reperfusion. Rats were pretreated for 10 days, males with testosterone and females with estradiol and injuries from those hearts were compared to the hearts where both drugs were applied to the isolated hearts directly. The myocardial injuries were determined by changes in coronary flow, incidence and duration of arrhythmias and lactate dehydrogenase release rates used as markers for level of cardiac injury during reperfusion. Coronary flow in the hearts of animals pretreated with estradiol during reperfusion increased by 68.7+/-3.6% (P<0.001) and in those pretreated with testosterone by 50.1+/-2.1% (P<0.05) vs. control hearts. Lactate dehydrogenase release rates decreased in the hearts of animals pretreated with estradiol by 55.7+/-1.9% (P<0.01) vs. controls and by 58.8+/-3.0 (P<0.01) vs. directly applied estradiol. Duration of ventricular fibrillation decreased after 10 days application of drugs, from 9.42+/-0.81 min to 4.58+/-0.93 min (P<0.05) with estradiol and from 9.19+/-1.05 min to 4.65+/-0.51 min (P<0.05) with testosterone. The duration of heart arrest decreased in 10 days application of testosterone from 2.42+/-0.16 min to 20.0+/-12.26 s (P<0.01). Hearts from animals pretreated for 10 days with estradiol showed more cardioprotective effects during reperfusion than those pretreated with testosterone. Testosterone pretreatment, despite being less effective in cardioprotection than estradiol, improved coronary flow and decreased arrhythmias as effectively as estradiol.

Hypoxic and pharmacological preconditioning preserves vasomotor response of porcine coronary artery.

Vasomotor response of the coronary artery depends on both endothelial and smooth muscle cells. Response is altered by hypoxia-reoxygenation-induced damages. Hypoxic preconditioning and pharmacological preconditioning as well can prevent these alterations. We compared the effectiveness of both types of preconditioning against hypoxia-reoxygenation-induced changes in vasomotor response of the isolated artery. Porcine arterial rings (3-4 mm wide) were cut from the left anterior descending porcine coronary artery and placed in Krebs-Henseleit solution. In order to obtain control response of the arteries, we contracted arterial rings with 20 mM KCl before ("standard contraction") and after 60-min hypoxia and 30-min reoxygenation. In other groups, nitric oxide-synthase and cyclooxygenase were inhibited. Then, the rings were pre-contracted with U46619 and relaxed by cumulative addition of the substance P. Contractions and relaxations of non-preconditioned and hypoxically or pharmacologically preconditioned rings were compared. Hypoxic preconditioning was performed by two periods of 5-min hypoxia and 10-min reoxygenation. For pharmacological preconditioning, we used application of adenosine, adrenaline, acetylcholine and angiotensin II. Analysis was performed with one-way ANOVA, followed by Dunnett's Multiple Comparison Test. After hypoxia-reoxygenation, in non-preconditioned rings KCl-induced contractions were significantly increased compared to standard contraction. Relaxations of hypoxically and pharmacologically preconditioned rings (expressed as percentages of U46619-induced pre-contraction) were significantly decreased (p < 0.01) compared to hypoxic but not to normoxic rings. Hypoxic and pharmacological preconditioning may preserve contraction and endothelium-dependent relaxation of porcine coronary artery after long-lasting hypoxia-reoxygenation.

Tezosentan inhibits both equinatoxin II and endotelin-1 induced contractions of isolated porcine coronary artery in a similar way.

In the present study we examined the endothelium-dependent mechanism in the constriction of the isolated porcine coronary artery induced by Equinatoxin II (EqT II). EqT II is a polypeptide isolated from the sea anemone (Actinia equina, L.). Contractions induced by endothelin-1 (ET-1) were compared with the contractions induced by EqT II. The force of contraction induced by 100 nM EqT II reached only 30% of the force of contraction induced by 100 nM ET-1. EC50 for ET-1 was 5.14 nM, and for EqT II 101.1 nM. The effects of tezosentan, an endothelin ETA/B receptor antagonist, on contractions induced by either ET-1 or EqT II were compared. Tezosentan inhibited both ET-1 and, to a lesser extent, EqT II-induced contractions of isolated porcine coronary artery. Our present results confirm the involvement of endothelium in the EqT II-induced contractions of coronary arteries. The mode of action of tezosentan upon EqT II-induced contractions indicate that besides its pore-forming effect in the membranes, endothelium, and specifically endothelin-dependent mechanisms, are very important components of the toxin constrictory effects.

Nicardipine diminished equinatoxin II-induced decrease of coronary flow in isolated rat and pig hearts.

Equinatoxin II (EqT II) is a basic, cardiotoxic polypeptide. The vasoconstrictory effect of the toxin on isolated porcine coronary arteries was diminished by nicardipine, an L-type calcium channel antagonist. A comparison was made of the effects of EqT II alone and EqT II in the presence of nicardipine on the coronary flow in porcine and rat hearts isolated according to Langendorff's method. In both models EqT II decreased coronary flow in a dose-dependent manner and there were no statistically significant differences between the two models (p>0.05). However, 1 M nicardipine diminished the effects of EqT II on coronary flow in isolated porcine hearts more than in isolated rat hearts (p<0.05). The results suggest that the activation of L-type calcium channels is one of the mechanisms involved in the lowering of coronary flow induced by EqT II.

Thermal conductivity of the porcine heart tissue.

The porcine heart was used as a model for studying the thermal changes in myocardium at cooling and re-warming during open heart surgery. A section of the heart septum was excised and tissue was cut into two similar square slices. The same shape of the tissue, cut from the surface from the upper lateral wall of the left ventricle, covered with epicardium and fat, was taken for another measurement. A thin (<0.5 mm) square thermal source of the same length of the side as the tissue samples was put between the two slices of tissue. This set was placed in the middle of two identical copper cylinders (2r=50 mm, height=55 mm) used to keep the outer side of the specimen at controlled room temperature. Thermal conductivity of the heart tissue was determined at controlled thermal power, and known difference of the temperature at the edge of the tissue and at the middle of the heater, when steady state was reached. Thermal conductivity calculated from the temperature difference and the geometry of heater and samples was 0.75 W/m.K for septal heart tissue, and 0.60 W/m.K for the lateral wall ventricle tissue with epicardium and fat.

Lowering of the coronary flow in isolated rat heart by equinatoxin II depends upon extracellular Ca2+ concentration.

Equinatoxin II (EqT II) is a basic polypeptide toxin from the sea anemone Actinia equina (L.). Its LD50 in mice is 33 g/kg. The cause of death after intravenous application has been attributed to the circulatory failure resulting in the cardiotoxic effects. In Langendorff's rat and guinea-pig heart preparations EqT II caused dose dependent decrease in the coronary flow (CF). Morphologic changes of different cell cultures incubated with EqT II are the result of Ca2+ entry through the newly formed discrete pores. Pores in the cell membranes are composed of the toxin oligomeres. In the present study we tried to evaluate the dependence of vasoconstrictor effects of EqT II on isolated rat hearts upon the Ca2+ concentration in the perfusion solution. EqT II did not affect the CF in the group without Ca2+. The strongest effect was observed in the group with 1.5 mM Ca2+ where the CF decreased to 7.7±7 %. The results of our experiments indicate that the effects of EqT II on CF depend on Ca2+ concentration in the extracellular solution.