The effect of thrombin on the dynamic exchange between intraplatelet and extraplatelet fibrinogen

We examined the distribution of platelet fibrinogen and the exchange between intra- and extra-platelet fibrinogen in unstimulated and thrombin-stimulated platelets. In unstimulated platelets 60% of platelet fibrinogen was found in the soluble platelet fraction and 40% in the insoluble one. In platelets activated with thrombin, changes took place in the distribution of intraplatelet fibrinogen but not in the total fibrinogen content. At 0.5 U/ml of thrombin the fibrin(ogen) content of the insoluble and soluble fractions was approximately 80% and 20%, respectively. When we evaluated how extraplatelet fibrinogen affects the content and distribution of intraplatelet fibrinogen, we found that when unlabelled fibrinogen was added to unstimulated and thrombin-stimulated platelets the content and distribution of intraplatelet fibrinogen remained unaltered. However, when ¹²⁵I-fibrinogen was added, it was incorporated into unstimulated and thrombin-stimulated platelets. In unstimulated platelets, 70% of the incorporated ¹²⁵I-fibrinogen was in the soluble fraction and 30% in the insoluble. In thrombin-stimulated platelets the distribution of the incorporated ¹²⁵I-fibrinogen was 62% and 38% in soluble and insoluble fractions respectively. MoAb to GPIIb–IIIa produced 80% and 60% inhibition of ¹²⁵I-fibrinogen incorporation by unstimulated and thrombin-stimulated platelets. Our data showed dynamic exchange between intraplatelet and extraplatelet fibrinogen both in unstimulated and thrombin-stimulated platelets mediated mainly by GPIIb–IIIa.     

LRP1 Gene Polymorphisms Are Associated With Premature Risk of Cardiovascular Disease in Patients With Familial Hypercholesterolemia

INTRODUCTION AND OBJECTIVES: LRP1 gene overexpression in atherosclerotic plaque is associated with increased lipid uptake through the vascular wall. The aim of the study was to analyze whether LRP1 modulates the genetic risk of developing premature cardiovascular disease in familial hypercholesterolemia, using single nucleotide polymorphism association analysis. METHODS: Ten polymorphisms of the LRP1 gene (rs715948, rs1799986, rs1800127, rs7968719, rs1800176, rs1800194, rs1800181, rs1140648, rs1800164, and rs35282763) were genotyped in 339 patients (77 with premature cardiovascular disease and 262 without) in the SAFEHEART study. RESULTS: The c.677C>T (rs1799986) polymorphism showed a significant association with premature cardiovascular disease after adjusting by sex, age, body mass index, and the effect of the low-density lipoprotein receptor mutation in the dominant model (CT+TT vs CC: odds ratio=1.94; 95% confidence interval, 1.08-3.48; P=.029). Similar results were observed after increasing the sample to 648 subjects (133 with premature cardiovascular disease vs 515 without [odds ratio=1.83; 95% confidence interval, 1.16-2.88; P=.011]). CONCLUSIONS: The c.677C>T polymorphism is associated with increased rates of premature cardiovascular disease in familial hypercholesterolemia. Although we were unable to show that this polymorphism was involved in the alteration of normal mRNA splicing patterns, the possibility that it is in strong linkage disequilibrium with another functional polymorphism cannot be ruled out and would explain the cause-effect relationship with cardiovascular disease risk in this population. Further studies are needed to replicate the results and to localize the putative genetic variants associated with this polymorphism. Full English text available from:www.revespcardiol.org.     

Effect of chronic exposure to inorganic arsenic on intestinal cells

Chronic exposure to inorganic arsenic (As)—As(III) + As(V)—is associated with type 2 diabetes, vascular diseases and various types of cancer. Although the oral route is the main way of exposure to inorganic As, the adverse gastrointestinal effects produced by chronic exposure are not well documented. The aim of the present study is to evaluate the effect of chronic exposure to As(III) on the intestinal epithelium. For this purpose, NCM460 cells, non‐transformed epithelial cells from the human colon, were exposed to As(III) (0.01‐0.2 mg/L) for 6 months and monitored for acquisition of a tumor‐like phenotype. Secretion of matrix metalloproteinases, histone modifications (H3 acetylation), hyperproliferation capacity, formation of floating spheres, anchorage‐independent growth, release of cytokine interleukin‐8 and expression of relevant genes in colon tumorigenesis were assessed. The results show a maintained proinflammatory response from the beginning, with an increase in interleukin‐8 secretion (≤570%). Downregulation of CDX1 and CDX2 was also observed. After 14 weeks of exposure, cells presented marked increases in matrix metalloproteinase‐2 secretion and histone modifications. As(III)‐treated cells were hyperproliferative, grew in low‐serum media and were able to form free‐floating spheres. Overall, these data suggest that exposure of human colon epithelial cells to As(III) facilitates acquisition of transformed cell characteristics.     

Health in all policies, a challenge for public health in Spain. SESPAS report 2010

The objective of SESPAS Report 2010 is to enhance the incorporation of the principle of Health in all Policies in public health in Spain. The fundamental principle behind this slogan is very simple: Health is strongly influenced by the environment, how we live, work, eat, walk or enjoy our leisure time. Moreover, these living conditions depend not only on individual decisions but are determined by social, cultural, economic or environmental factor. Consequently, policy decisions that influence the health of people not just those related to services or health policy, but primarily those taken in other public, private, political and civic contexts. SESPAS Report 2010 has four parts. It begins with and introductory chapter on the challenges of incorporating the principle of Health in all Policies in public health. The second part consists of several articles of reflection on the relationship between the health care system and public health. The third part focuses on cross-sectoral public health policies. The report ends with several articles on cross-cutting issues such as public health education, information, research, evaluation and ethics in public health policies.     

Voltage-gated k+ channel block by catechol derivatives: defining nonselective and selective pharmacophores

High-throughput screening led to the identification of a 3-norbornyl derivative of catechol called 48F10 (3-bicyclo[2.2.1]hept-2-yl-benzene-1,2-diol) as a Kv2.1 K(+) channel inhibitor. By virtue of the involvement of Kv2.1 channels in programmed cell death, 48F10 prevents apoptosis in cortical neurons and enterocytes. This uncharged compound acts with an apparent affinity of 1 muM at the tetraethylammonium (TEA) site at the external mouth of the Kv2.1 channel but is ineffective on Kv1.5. Here we investigated the basis of this selectivity with structure-activity studies. We find that catechol (1,2-benzenediol), unlike 48F10, inhibits Kv2.1 currents with a Hill coefficient of 2 and slows channel activation. Furthermore, this inhibition, which requires millimolar concentrations, is unaffected by external TEA or by mutation of the external tyrosine implicated in channel block by TEA and 48F10. In addition, catechol does not distinguish between Kv2.1 and Kv1.5. Thus, catechol acts at conserved sites that are distinct from 48F10. We also tested 11 catechol derivatives based on hydrocarbon adducts including norbornyl substructures, a 48F10 isomer, and a 48F10 diastereomer. These compounds are more potent than catechol, but none replicated the marked selectivity of 48F10 for Kv2.1 over Kv1.5. We conclude that the targeting of 48F10 to the TEA site at the external mouth of the Kv2.1 pore and away from other sites involved in nonselective Kv channel block by catechol requires the norbornyl group in a unique position and orientation on the catechol ring.     

Coping strategies in stress and sources of professional reward in specialized physicians of the Valencia Community. A study with semi-structured interviews

BACKGROUND: The professionals in the medical field are particularly exposed to psychological risk factors which may affect their quality of life. Identification of stress coping strategies and the sources of professional rewards would afford the possibility of implementing preventive measures aimed a moderating the negative effect of these risk factors. The objectives of this study are to identify the stress coping strategies that are used by specialised doctors from six public hospitals of the Valencian Community, and to describe their sources of work reward and job satisfaction. METHODS: A qualitative study conducted by means of quasi-structured individual interviews of 47 specialists employed at six public hospitals in the province of Valencia. The interviews were taped and subsequently transcribed. An analysis was made of the substance of the opinions expressed. RESULTS: The coping strategies mentioned most often by the physicians interviewed, analyzed overall, are those focused on the emotions, specifically, disconnecting conduct and seeking social emotional support. However, when confronted with specific stressful factors in daily practice, the strategies most often employed as those focused on the problem. A major part of the physicians surveyed state not having any work reward. Among those who do state finding some aspects gratifying, top mention is made of their salary, personal satisfaction related to being in the medical field being ranked second. CONCLUSIONS: Including training related to active stress coping strategies in the professional curriculum of physicians could heighten their personal resources for dealing with stress. Organizational changes should additionally be made to increase their work rewards.     

Intrepid: Second nursing cycle. First step, first desire in European Spain

When we started to write this article for ROL the first question which confronted us was first step? Why? The beginning of second cycle studies in 1998 did not correspond to any European desire, but rather consolidated a real desire which Spanish Nursing had: attain the highest possible academic title through growth inside the nursing discipline itself, having as an objective to place nursing in equal conditions as the majority of titles in the Spanish university system. This meant it was necessary to carry out research and investigation inside one's own scientific field, develop future professionals, administrate under equal conditions, and specifically consolidate a way deserving of one who bears responsibility over health care.     

Physical load and psychological demand at work during pregnancy and preterm birth

OBJECTIVES: To evaluate the effect of physical workload and psychological demand on all preterm births, and to determine whether these risk factors have the same effect on different types of preterm birth (moderate versus very preterm birth) and different modes of delivery onset (spontaneous versus indicated preterm birth). METHODS: A case-control study was carried out in two public general hospitals in the Valencia Region, Spain. All preterm births (228) which occurred between 22 and 36 completed weeks of amenorrhea and 348 controls of 37 or more completed weeks of amenorrhea were included. The information was collected by interviewing women within 2 days of their giving birth. Physical workload, psychological demand, weekly working hours and daily time spent commuting between home and work were used as explanatory variables. A polytomous logistic regression was carried out. RESULTS: Exposure to medium or high level physical workload increases the risk of preterm birth, with an adjusted odds ratio (OR) of 1.59 and 2.31, respectively. The risk of moderate preterm birth was greater in women with a medium or high level of physical workload, OR: 1.73 and 2.35, respectively. The same trend was observed for very preterm birth. Physical workload showed a different effect on spontaneous and indicated preterm birth. The exposure to medium and high level physical workload increases the risk of indicated preterm birth, with an OR of 2.74 and 3.88, respectively. The same trend was seen in the case of spontaneous preterm birth. Psychological demands were not associated with preterm birth. CONCLUSIONS: High physical exertion increases the risk of preterm birth in Spain. The magnitude of the effect of physical workload on moderate and very preterm birth is similar, but is higher on indicated preterm birth than on spontaneous preterm birth. Psychological demands show no effect on the risk of preterm birth.     

Comparison of three different volumes of mepivacaine in axillary plexus block using multiple nerve stimulation

Background. The multiple injection technique for axillary block,in which the four distal nerves of the plexus are located bya nerve stimulator and separately injected, has been shown toprovide a high success rate and a short onset time. This randomizeddouble-blind study was conducted to compare the effectivenessof three different volumes of mepivacaine 10 mg ml^–1 inpatients undergoing elective distal upper limb surgery underaxillary brachial plexus block with the four-nerve approach.The number of complete sensory blocks was the primary efficacyvariable. Methods. A total of 114 adult patients were randomly allocatedto receive 36 (n=38), 28 (n=38), and 20 ml (n=38) of mepivacaine10 mg ml^–1. In each group, volumes were equally distributedin the four nerve territories. In all patients, performancetime, latency time, block characteristics, need of supplementaryblocks, tourniquet tolerance, duration of analgesia, and complicationswere recorded. Results. Complete sensory block was obtained in 97% of patientsreceiving a volume of 36 ml, 97% of those receiving 28 ml, and94% of those receiving 20 ml. One patient in the group of 28ml and five patients in the group of 20 ml experienced painon inflation of the tourniquet. Two months after surgery, nocase of postoperative neurological dysfunction was observed. Conclusions. The three volumes (38, 28, and 20 ml) of mepivacaine10 mg ml^–1 ensured a similar and high percentage of completesensory blocks in axillary brachial plexus anaesthesia withnerve stimulation involving the location of four motor responses. Br J Anaesth 2003; 91: 519–24