Two research paths for probing the roles of oxygen in metabolic regulation

Tissues such as skeletal and cardiac muscles must sustain very large-scale changes in ATP turnover rate during equally large changes in work. In many skeletal muscles these changes can exceed 100-fold. Examination of a number of cell and whole-organism level systems identifies ATP concentration as a key parameter of the interior milieu that is nearly universally 'homeostatic'; it is common to observe no change in ATP concentration even while change in its turnover rate can increase or decrease by two orders of magnitude or more. A large number of other intermediates of cellular metabolism are also regulated within narrow concentration ranges, but none seemingly as precisely as is [ATP]. In fact, the only other metabolite in aerobic energy metabolism that is seemingly as 'homeostatic' is oxygen - at least in working muscles where myoglobin serves to buffer oxygen concentrations at stable and constant values at work rates up to the aerobic maximum. In contrast to intracellular oxygen concentration, a 1:1 relationship between oxygen delivery and metabolic rate is observed over biologically realistic and large-magnitude changes in work. The central regulatory question is how the oxygen delivery signal is transmitted to the intracellular metabolic machinery. Traditional explanations assume diffusion as the dominant mechanism, while proponents of an ultrastructurally dominated view of the cell assume an intracellular perfusion system to account for the data which have been most perplexing to metabolic biochemistry so far: the striking lack of correlation between changes in pathway reaction rates and changes in concentrations of pathway substrates, including oxygen and pathway intermediates.

Vascular changes after cardiopulmonary bypass and ischemic cardiac arrest: roles of nitric oxide synthase and cyclooxygenase

Cardiac surgery involving ischemic arrest and extracorporeal circulation is often associated with alterations in vascular reactivity and permeability due to changes in the expression and activity of isoforms of nitric oxide synthase and cyclooxygenase. These inflammatory changes may manifest as systemic hypotension, coronary spasm or contraction, myocardial failure, and dysfunction of the lungs, gut, brain and other organs. In addition, endothelial dysfunction may increase the occurrence of late cardiac events such as graft thrombosis and myocardial infarction. These vascular changes may lead to increased mortality and morbidity and markedly lengthen the time of hospitalization and cost of cardiac surgery. Developing a better understanding of the vascular changes operating through nitric oxide synthase and cyclooxygenase may improve the care and help decrease the cost of cardiovascular operations.

Gap junctions in cells of the immune system: structure, regulation and possible functional roles

Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs) which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.

Reliability and validity of the interactive observation scale for psychiatric inpatients applied by nursing aides in daily ward practice

The main characteristic of the nursing Interactive Observation Scale for Psychiatric Inpatients (IOSPI) is the necessity of interaction between raters and patients during assessment. The aim of this study was to evaluate the reliability and validity of the scale in the "real" world of daily ward practice and to determine whether the IOSPI can increase the interaction time between raters and patients and influence the raters' opinion about mental illness. All inpatients of a general university hospital psychiatric ward were assessed daily over a period of two months by 9 nursing aides during the morning and afternoon shifts, with 273 pairs of daily observations. Once a week the patients were interviewed by a psychiatrist who filled in the Brief Psychiatric Rating Scale (BPRS). The IOSPI total score was found to show significant test-retest reliability (interclass correlation coefficient = 0.83) and significant correlation with the BPRS total score (r = 0.69), meeting the criteria of concurrent validity. The instrument can also discriminate between patients in need of further inpatient treatment from those about to be discharged (negative predictive value for discharge = 0.91). Using this scale, the interaction time between nursing aides and patients increased significantly (t = 2.93, P<0.05) and their opinion about the mental illness changed. The "social restrictiveness" factor of the opinion scale about mental illness showed a significant reduction (t = 4.27, P<0.01) and the "interpersonal etiology" factor tended to increase (t = 1.98, P = 0.08). The IOSPI was confirmed as a reliable and valid scale and as an efficient tool to stimulate the therapeutic attitudes of the nursing staff.

Nurse Competence of Graduating Nursing Students

The competence of graduating nursing students is an important issue in health care as it is related to professional standards, patient safety and the quality of nursing care. Many changes in health care lead to increased demand with respect to nurses’ competence as well the number of nurses. The purpose of this empirical study was to i) describe the nurse competence areas of nursing students in Europe, ii) evaluate the nurse competence of graduating nursing students, iii) identify factors related to the nurse competence, and to iv) assess the congruence between graduating nursing students’ self-assessments and their mentors’ assessments of students’ nurse competence. The study was carried out in two phases: descriptive phase and evaluation phase. The descriptive phase focused on describing the nurse competence areas of nursing students in Europe with the help of a literature review (n=10 empirical studies and n=4 additional documents). Thematic analysis was used as the analysis method. In the evaluation phase, the nurse competence with particular focus on nursing skills of graduating nursing students (n=154) was assessed. In addition, factors related to the nurse competence were examined. Also, the congruence between graduating nursing students’ self-assessments and their mentors’ assessments of students’ nurse competence was evaluated by comparing graduating nursing students’ self-assessments with the assessments by their mentors (n=42) in the final clinical placement in four university hospitals. Descriptive statistics and inferential statistics were used to analyse the data. Based on the results, the nurse competence of nursing students in Europe consists of nine main competence areas: (1) professional/ethical values and practice, (2) nursing skills and interventions, (3) communication and interpersonal skills, (4) knowledge and cognitive ability, (5) assessment and improving quality in nursing, (6) professional development, (7) leadership, management and teamwork, (8) teaching and supervision, and (9) research utilization. Graduating nursing students self-assessed their nurse competence as good. However, when graduating nursing students’ nurse competence was assessed by their mentors, the results were poorer. Readiness for practice based on nurse education, pedagogical atmosphere on the ward, supervisory relationship between student and mentor and being in paid work in health care at the moment of the study were the most significant factors related to the nurse competence. Conclusions: Nurse competence can be evaluated with a scale based on self-assessment, but other evaluation methods could be used alongside to ensure that nurse competence can be completed and evaluated critically. Practical implications are presented for nurse education and nursing practice. In future, longitudinal research is needed in order to understand the development of nurse competence during nurse education and the transition process from a nursing student to a professional nurse.

MARKETING COMMUNICATIONS IN B2B COMPANIES – The Roles of Marketing Communication Tools in the Digital Age

Marketing communications has gone through significant changes during the last decades and new online tools have been leading this change for the last decade. Now, in the digital age, if wanting to be successful companies need to experiment new things and seize the opportunities online provides and adapt to the new environment. However, during this time the marketing communication mix and the meanings given to the various components of it have not changed dramatically, and personal selling, direct marketing, sales promotion, advertising and public relations activities are still regarded as important tools in the marketing communications mix. The purpose of this study was to examine business-to-business marketing communications and the tools used by companies in their marketing communications efforts in the digital age and in a global environment. The research questions dealt with the marketing communication tools and their roles as well as the role of online marketing communication and the way it has shaped the field of b2b marketing communications. In order to answer these questions, qualitative approach was chosen and the data was collected by theme interviews with six representatives of Finnish global companies from the b2b sector being interviewed. The theoretical framework covers the general field of b2b marketing communications and its main elements. The online environment as well as the concept of a global marketplace and integrated approach to marketing communication activities is also discussed. The theory was supported by the interviews regarding the activities and roles of the marketing communication tools and both theory as well as the interviews found personal selling to be a vital tool. However, the importance of online has grown and online marketing activities have risen right next to personal selling. The use of analytics and marketing automation was found to be of great interest in the interviews and they were seen as a growing domain in b2b marketing communications. The importance of targeted and personalised messages from relevant medias was a repeating theme as was the customer-centric approach in marketing communication activities. Also, offline and online tools and channels were seen as something that should be treated together as an entity rather than as separate activities. Relevant content created according to the needs of the customer with the gathered data from analytics were seen as the future of b2b marketing communications. Online has added its input to the more traditionally perceived tools and they are executed within the framework of the digital age. Nevertheless, even though online has increased its presence in the b2b marketing communications mix, the more traditionally perceived marketing communication tools, especially personal selling, have not lost their meaning or place in the b2b marketing communication mix.

Nucleotide-sugar transporters: structure, function and roles in vivo

The glycosylation of glycoconjugates and the biosynthesis of polysaccharides depend on nucleotide-sugars which are the substrates for glycosyltransferases. A large proportion of these enzymes are located within the lumen of the Golgi apparatus as well as the endoplasmic reticulum, while many of the nucleotide-sugars are synthesized in the cytosol. Thus, nucleotide-sugars are translocated from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum by multiple spanning domain proteins known as nucleotide-sugar transporters (NSTs). These proteins were first identified biochemically and some of them were cloned by complementation of mutants. Genome and expressed sequence tag sequencing allowed the identification of a number of sequences that may encode for NSTs in different organisms. The functional characterization of some of these genes has shown that some of them can be highly specific in their substrate specificity while others can utilize up to three different nucleotide-sugars containing the same nucleotide. Mutations in genes encoding for NSTs can lead to changes in development in Drosophila melanogaster or Caenorhabditis elegans, as well as alterations in the infectivity of Leishmania donovani. In humans, the mutation of a GDP-fucose transporter is responsible for an impaired immune response as well as retarded growth. These results suggest that, even though there appear to be a fair number of genes encoding for NSTs, they are not functionally redundant and seem to play specific roles in glycosylation.

Roles of calcium and IP3 in impaired colon contractility of rats following multiple organ dysfunction syndrome

The purpose of the present study was to explore changes in rat colon motility, and determine the roles of calcium and inositol (1,4,5)-triphosphate (IP3) in colon dysmotility induced by multiple organ dysfunction syndrome (MODS) caused by bacteria peritonitis. The number of stools, the contractility of the muscle strips and the length of smooth muscle cells (SMC) in the colon, the concentration of calcium and IP3 in SMC, and serum nitric oxide were measured. Number of stools, fecal weight, IP3 concentration in SMC and serum nitric oxide concentration were 0.77 ± 0.52 pellets, 2.51 ± 0.39 g, 4.14 ± 2.07 pmol/tube, and 113.95 ± 37.89 µmol/L, respectively, for the MODS group (N = 11) vs 1.54 ± 0.64 pellets, 4.32 ± 0.57 g, 8.19 ± 3.11 pmol/tube, and 37.42 ± 19.56 µmol/L for the control group (N = 20; P < 0.05). After treatment with 0.1 mM acetylcholine and 0.1 M potassium chloride, the maximum contraction stress of smooth muscle strips, the length of SMC and the changes of calcium concentration were 593 ± 81 and 458 ± 69 g/cm³, 48.1 ± 11.8 and 69.2 ± 15.7 µM, 250 ± 70 and 167 ± 48%, respectively, for the control group vs 321 ± 53 and 284 ± 56 g/cm³, 65.1 ± 18.5 and 87.2 ± 23.7 µM, 127 ± 35 and 112 ± 35% for the MODS group (P < 0.05). Thus, colon contractility was decreased in MODS, a result possibly related to reduced calcium concentration and IP3 in SMC.

Roles of mitogen-activated protein kinases and angiotensin II in renal development

Experimental and clinical evidence suggests that angiotensin II (AII) participates in renal development. Renal AII content is several-fold higher in newborn rats and mice than in adult animals. AII receptors are also expressed in higher amounts in the kidneys of newborn rats. The kidneys of fetuses whose mother received a type 1 AII receptor (AT1) antagonist during gestation present several morphological alterations. Mutations in genes that encode components of the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Morphological changes were detected in the kidneys of 3-week-old angiotensin-deficient mice. Mitogen-activated protein kinases (MAPKs) are important mediators that transduce extracellular stimuli to intracellular responses. The MAPK family comprises three major subgroups, namely extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinases (JNK), and p38 MAPK (p38). Important events in renal growth during nephrogenesis such as cellular proliferation and differentiation accompanied by apoptosis on a large scale can be mediated by MAPK pathways. A decrease in glomerulus number was observed in embryos cultured for 48 and 120 h with ERK or p38 inhibitors. Many effects of AII are mediated by MAPK pathways. Treatment with losartan during lactation provoked changes in renal function and structure associated with alterations in AT1 and type 2 AII (AT2) receptors and p-JNK and p-p38 expression in the kidney. Several studies have shown that AII and MAPKs play an important role in renal development. However, the relationship between the effects of AII and MAPK activation on renal development is still unclear.

Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP8-37) and ADM receptor antagonist (ADM22-52) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.

Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc) and progesterone (OVP, 1.7 mg·kg-1·day-1,sc). We assessed Na+ and Cl-fractional excretion (FENa+ and FECl-, respectively) and renal and plasma catecholamine release concentrations. FENa+, FECl-, water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+, FECl-, water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Disentangling the effects of insomnia and night work on cardiovascular diseases: a study in nursing professionals

Cardiovascular diseases (CVDs) are known to be associated with poor sleep quality in general populations, but they have not been consistently associated with specific work schedules. Studies of CVD generally do not simultaneously consider sleep and work schedules, but that approach could help to disentangle their effects. We investigated the association between insomnia and a self-reported physician diagnosis of CVD in day and night workers, considering all sleep episodes during nocturnal and diurnal sleep. A cross-sectional study was conducted in 1307 female nursing professionals from 3 public hospitals, using baseline data from the “Health and Work in Nursing - a Cohort Study.” Participants were divided into two groups: i) day workers with no previous experience in night shifts (n=281) and whose data on insomnia were related to nocturnal sleep and ii) those who worked exclusively at night (n=340) and had data on both nocturnal and diurnal sleep episodes, as they often sleep at daytime. Multiple logistic regression analysis was performed. Among day workers, insomnia complaints increased the odds of CVD 2.79-fold (95% CI=1.01-6.71) compared with workers who had no complaints. Among night workers, reports of insomnia during both nocturnal and diurnal sleep increased the odds of reported CVD 3.07-fold (95% CI=1.30-7.24). Workers with insomnia had similar probabilities of reporting CVD regardless of their work schedule, suggesting a relationship to insomnia and not to night work per se. The results also highlighted the importance of including evaluation of all sleep episodes (diurnal plus nocturnal sleep) for night workers.