Electronic cigarettes and obstetric outcomes: a prospective observational study.

OBJECTIVE: To compare the obstetric outcomes and socio-demographic factors in electronic cigarette (EC) users with cigarette smokers and non-smokers in pregnancy. DESIGN: Prospective observational cohort study. SETTING: A large urban maternity hospital delivering almost 8500 infants per year. POPULATION: Pregnant women attending for antenatal care. METHODS: Electronic cigarette users at time of booking history were prospectively identified. Maternal and neonatal outcomes were compared with those of pregnant smokers and non-smokers. Multiple logistic regression analysis was performed to estimate the association between the explanatory variables and birthweight. MAIN OUTCOMES MEASURES: Infant birthweight, gestation at delivery, incidence of low birthweight. RESULTS: A total of 218 women with exclusive EC use and 195 women with dual use of both cigarettes and EC, had a live birth during the study period. EC users were of higher socio-economic status than smokers. Infants born to EC users had a mean birthweight of 3470 g (± 555 g), which was similar to that of non-smokers (3471 ± 504 g, P = 0.97) and significantly greater than that of smokers (3166 ± 502 g, P < 0.001). The mean birth centile of EC users was similar to non-smokers (51st centile versus 47th centile, P = 0.28) and significantly greater than that of smokers (27th centile, P < 0.001). Dual users had a mean birthweight and birth centile similar to that of smokers. CONCLUSION: The birthweight of infants born to EC users is similar to that of non-smokers, and significantly greater than cigarette smokers. Dual users of both cigarettes and EC have a birthweight similar to that of smokers. TWEETABLE EXTRACT: Birthweight of infants born to electronic cigarette users appears to be similar to that of non-smokers.

Antenatal prediction of fetal macrosomia in pregnancies affected by maternal pre-gestational diabetes.

AIMS: Higher rates of fetal macrosomia may occur in infants of women with pre-gestational diabetes compared with non-diabetic controls. Antenatal predication of fetal macrosomia remains challenging. Ultrasound over-estimated fetal weight could result in over-classification of fetuses as macrosomic with corresponding inappropriate clinical interventions. Previously we had studied a measurement - the anterior abdominal wall measurement (AAW) - to predict fetal macrosomia in fetal estimation of weight. The purpose of the study was to study whether specific third trimester ultrasound measurements with measures of glycaemic control (HbA1c) predicted macrosomia in babies born to women with pre-gestational diabetes. In particular, a new variant of this measurement (fetal anterior abdominal wall thickness (AAW), abdominal circumference (AC) ratio: AAW:AC) was investigated. METHODS: This was a prospective cohort study in a tertiary referral maternity hospital. Serial growth scans including measurement of AAW and AC: AAW ratio was performed at 30, 33- and 36-weeks' gestation. Birth-weight data was collected, and macrosomia was defined as >90th centile based on gestational age and gender of the baby. Serial HbA1c as measured at the first antenatal visit, 14, 20- and 36-weeks' gestation were reported for this study. RESULTS: Of the 416 pregnancies analyzed, mean maternal age was 33.3 years. One in five women were primigravida's. The mean birthweight was 3548 g (+/- 581 g), of which 142 (34%) babies were classified as macrosomic. The median gestational age at delivery was 383 weeks (314 - 402 weeks). There were 37 (9%) babies born preterm at <37 weeks' gestation. Mean AC measurements in fetuses that would be born with macrosomia compared with those with a non-macrosomic birth weight were 282 mm vs. 266 mm at 30 weeks, 318.3 mm vs. 297 mm at 33 weeks and 350 mm vs. 325 mm at 36 weeks' gestation (all p < .001). Mean AAW measurements in macrosomic fetuses compared with normal size fetuses were 3.7 mm vs. 3.3 mm at 30 weeks, 4.9 mm vs 4.3 mm at 33 weeks and 5.9 mm vs. 5.3 mm at 36 weeks' gestation (all p < .001). The mean AC: AAW was 0.01 for both normal and macrosomic fetuses at 30 weeks. There was no clinical or statistical difference in AC:AAW ratios between non-macrosomic and macrosomic infants. Binary logistic regression showed that AC at 36 weeks was most predictive of macrosomia (76.5%), followed by AAW at 30 weeks (68.5%). Using a combination of HbA1c booking, 14, 20, 36 weeks and AAW 30, 33, 36 weeks and AC 30, 33, 36 weeks predicted macrosomia in 80.9%. The ratio of AC: AAW did not act as a useful antenatal clinical predictor of macrosomia at birth. CONCLUSIONS: Abdominal circumference at 36 weeks was the single best predictor of fetal macrosomia. A combined model of HbA1c, AC and AAW was the best antenatal predictor of macrosomia, with intriguing clinical possibilities in the possible prevention of maternal and fetal complications of macrosomia.

The effect of visual interventions on illness beliefs and medication adherence for chronic conditions: A scoping review of the literature and mapping to behaviour change techniques (BCTs).

BACKGROUND: Maintaining health with chronic conditions often involves taking multiple medications; however, approximately 50% of patients with chronic conditions are non-adherent to medication. Patients' illness beliefs inform health behaviour, including medication-taking. Research has shown that visuals accompanying health information increased patient comprehension and the accuracy of illness perceptions. To date, the influence of visuals on illness beliefs and medication adherence has not been comprehensively reviewed. OBJECTIVES: The review aimed to collate available literature on visualisation interventions for illness beliefs and medication adherence in chronic conditions and identify key intervention characteristics. METHODS: A scoping review was conducted according to recommended guidelines and the PRISMA-ScR statement. Searches used keywords relating to 'illness', 'visual', 'adherence', 'illness perception', 'intervention', and 'medication'. Six databases were searched from inception to 2019; reference-list searching provided additional articles. Articles were included if the study population had a chronic health condition, the intervention included a visual element, had a measure of illness beliefs or medication adherence. Data regarding intervention characteristics and outcomes were extracted. Behaviour change techniques (BCTs) were identified to provide further insight into intervention characteristics. RESULTS: Initially, 18,012 articles were identified. Screening led to 293 full-text articles, ultimately resulting in 45 studies for final analysis. Forty-four were quantitative studies, 1 was qualitative. Studies were grouped into those using visuals to conceptualise a condition, medication reminders and educational interventions. Almost two-thirds of visual interventions were effective post-intervention, 3 sustained post-1-year, although many studies only assessed impact immediately post-intervention. BCTs from 'Natural consequences', 'Socialsupport' and 'Feedback and monitoring' categories were prevalent in effective interventions for both outcomes, particularly the 'Salience of consequences' BCT. CONCLUSIONS: This comprehensive scoping review found that visual interventions can positively influence illness beliefs and medication adherence. These findings highlight the need to further evaluate the impact and sustainability of visual interventions.

Dual modulation of GIP and glucagon action by the low molecular weight compound 4-hydroxybenzoic acid 2-bromobenzylidene hydrazide.

AIM: The presence of functional gastric inhibitory polypeptide (GIP) receptors on adipocytes and knowledge that GIP plays a key role in fat deposition suggests a beneficial effect of GIP receptor antagonism in obesity and insulin resistance. GIP receptor antagonists studied to date are peptidic GIP analogues that must be administered by injection. METHODS: The present study has examined in vitro and in vivo metabolic actions of a low molecular weight GIP receptor modulator 4-hydroxybenzoic acid 2-bromobenzylidene hydrazide (4H2BH), suitable for oral administration. RESULTS: 4H2BH alone had no significant effect on cAMP production or insulin secretion from BRIN-BD11 cells. However, 4H2BH significantly inhibited GIP-mediated cAMP production and insulin secretion in vitro. 4H2BH also suppressed (p < 0.05 to p < 0.001) glucagon-induced elevations of cAMP generation and insulin secretion in BRIN-BD11 cells. However, 4H2BH had no effect on glucagon-like peptide-1 (GLP-1) mediated insulinotropic actions. Administration of 4H2BH to mice in combination with glucose and GIP significantly annulled the glucose-lowering actions of GIP. In agreement with this, 4H2BH completely annulled GIP-mediated insulin secretion. Combined injection of 4H2BH with glucagon also partially (p < 0.05 to p < 0.001) impaired glucagon-induced elevations in blood glucose and plasma insulin. 4H2BH had no effect on blood glucose or insulin levels when administered alone. CONCLUSION: These results indicate that 4H2BH has a dual effect of inhibiting GIP and glucagon-mediated biological actions. Given that hyperglucagonaemia is also a cardinal feature of type 2 diabetes, 4H2BH and related low molecular weight compounds appear worthy of further evaluation for therapeutic potential in obesity diabetes.

Microsomal prostaglandin E2 synthase 1 expression in basic calcium phosphate crystal-stimulated fibroblasts: role of prostaglandin E2 and the EP4 receptor.

OBJECTIVE: Basic calcium phosphate (BCP) crystals have been implicated in the pathogenesis of osteoarthritis (OA), in part because of their ability to upregulate cyclooxygenase and prostaglandin E(2) (PGE(2)) production. The aim of this work was to investigate the expression of terminal PGE(2) synthases and PGE(2) receptors (EP) in BCP crystal-stimulated fibroblasts. METHODS: Cultured fibroblasts were stimulated with BCP crystals in vitro. mRNA expression was measured by real-time polymerase chain reaction, and protein production by western blotting. RESULTS: Basal expression of microsomal prostaglandin E(2) synthase 1 (mPGES1) in osteoarthritic synovial fibroblasts (OASF) was found to be 30-fold higher than in human foreskin fibroblasts (HFF). BCP crystals increased mPGES1 expression fourfold in HFF, but not in OASF. EP4 expression was downregulated twofold by BCP crystals in OASF, but not in HFF. Exogenous PGE(2) also downregulated EP4 expression; this effect was blocked by co-administration of L-161,982, a selective EP4 antagonist. While administration of exogenous PGE(2) significantly upregulated mPGES1 expression in OASF, mPGES1 expression was threefold higher in the OASF treated with BCP crystals and PGE(2) as compared with OASF treated with PGE(2) alone. CONCLUSIONS: The differing effects of BCP crystals on mPGES1 expression in HFF and OASF may be explained by BCP crystal-induced EP4 downregulation in OASF, likely mediated via PGE(2). These data underline the complexity of the pathways regulating PGE(2) synthesis and suggest the existence of a compensatory mechanism whereby mPGES1 expression can be diminished, potentially reducing the stimulus for further PGE(2) production.

Mechanism of basic calcium phosphate crystal-stimulated matrix metalloproteinase-13 expression by osteoarthritic synovial fibroblasts: inhibition by prostaglandin E2.

OBJECTIVE: To determine the mechanism of matrix metalloproteinase (MMP)-13 upregulation in osteoarthritic synovial fibroblasts (OASF) in response to stimulation with basic calcium phosphate (BCP) crystals and to investigate the effect of prostaglandin (PG)E2 on BCP crystal-stimulated MMP expression. METHODS: Primary OASF were stimulated with BCP crystals; mRNA expression was measured by real-time reverse transcription-polymerase chain reaction and protein levels were assessed by Western blotting. RESULTS: BCP crystals upregulated MMP-13 mRNA expression over 20-fold and increased MMP-13 protein production in OASF. BCP crystal-stimulated MMP-13 mRNA expression was blocked by inhibition of the extracellular regulated kinase (ERK1/2) and p38 mitogen activated protein kinase (MAPK) pathways and inhibition of the activation of nuclear factor kappaB. Addition of exogenous PGE2 downregulated BCP crystal-stimulated MMP-13 expression. In contrast, PGE2 upregulated, and had no effect, on BCP crystal stimulated MMP-3 and MMP-1 mRNA expression, respectively. These effects of PGE2 were diminished by L-161,982, a selective EP4 receptor antagonist, and mimicked by CAY10399, a selective EP2 receptor agonist, and forskolin, an adenylate cyclase activator. CONCLUSIONS: These data suggest that BCP crystal induction of MMP-13 expression may involve the ERK1/2 and p38 MAPK pathways and activation of nuclear factor kappaB; this upregulation of MMP-13 may contribute to the accelerated cartilage breakdown in BCP crystal-associated osteoarthritis. PGE2 had contrasting effects on BCP crystal-stimulated MMP-3 and MMP-13 mRNA expression, mediated in an EP2/EP4/cAMP-dependent manner, suggesting that PGE2 may have beneficial as well as deleterious effects in BCP crystal-associated osteoarthritis.

Mechanism of basic calcium phosphate crystal-stimulated cyclo-oxygenase-1 up-regulation in osteoarthritic synovial fibroblasts.

OBJECTIVES: Basic calcium phosphate (BCP) crystals have been implicated in the pathogenesis of OA and stimulate cyclo-oxygenase (COX) expression and PGE(2) production. This study aimed to elucidate the mechanism of COX-1 up-regulation by BCP crystals and to characterize the PGs produced in OA synovial fibroblasts (OASFs) in response to BCP crystals. METHODS: OASFs were stimulated with BCP crystals in vitro. mRNA expression was measured by real-time PCR, PG production by EIA and protein production by western blot. RESULTS: Maximal (19-fold) up-regulation of COX-1 mRNA occurred 32 h after stimulation with BCP crystals; increased COX-1 protein production was also seen. At 32 h post-stimulation with BCP crystals, PGE(2) (and prostacyclin) production was COX-1 dependent. In contrast, maximal (17-fold) up-regulation of COX-2, with corresponding COX-2-dependent PG production, occurred 4 h after BCP crystal stimulation. There was no appreciable increased production of other PGs such as PGF(2alpha), thromboxane A(2) or cyclopentanone PGs including 15d-PGJ(2). Inhibition of protein kinase C (PKC) and extracellular regulated kinase 1/2 (ERK1/2) signal transduction pathways blocked BCP crystal-induced COX-1 mRNA expression. Bafilomycin A1, an inhibitor of intra-lysosomal BCP crystal dissolution, diminished BCP crystal-induced COX-1 mRNA expression. CONCLUSIONS: These findings indicate that BCP crystals can augment PG production in OASF through induction of COX-1 and COX-2. Intra-lysosomal BCP crystal dissolution and activity of the PKC and ERK1/2 signal transduction pathways are required for BCP crystal-induced COX-1 up-regulation. These data add to the evidence suggesting that the constitutive COX-1/inducible COX-2 concept is an over-simplification and suggest that non-selective COX inhibition may be preferable to COX-2 selective inhibition in BCP crystal-associated OA.

Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing.

AIM: The mechanisms underlying detection and transmission of sensory signals arising from visceral organs, such as the urethra, are poorly understood. Recently, specialized ACh-expressing cells embedded in the urethral epithelium have been proposed as chemosensory sentinels for detection of bacterial infection. Here, we examined the morphology and potential role in sensory signalling of a different class of specialized cells that express serotonin (5-HT), termed paraneurones. METHODS: Urethrae, dorsal root ganglia neurones and spinal cords were isolated from adult female mice and used for immunohistochemistry and calcium imaging. Visceromotor reflexes (VMRs) were recorded in vivo. RESULTS: We identified two morphologically distinct groups of 5-HT+ cells with distinct regional locations: bipolar-like cells predominant in the mid-urethra and multipolar-like cells predominant in the proximal and distal urethra. Sensory nerve fibres positive for calcitonin gene-related peptide, substance P, and TRPV1 were found in close proximity to 5-HT+ paraneurones. In vitro 5-HT (1 µm) stimulation of urethral primary afferent neurones, mimicking 5-HT release from paraneurones, elicited changes in the intracellular calcium concentration ([Ca2+ ]i ) mediated by 5-HT2 and 5-HT3 receptors. Approximately 50% of 5-HT responding cells also responded to capsaicin with changes in the [Ca2+ ]i . In vivo intra-urethral 5-HT application increased VMRs induced by urethral distention and activated pERK in lumbosacral spinal cord neurones. CONCLUSION: These morphological and functional findings provide insights into a putative paraneurone-neural network within the urethra that utilizes 5-HT signalling, presumably from paraneurones, to modulate primary sensory pathways carrying nociceptive and non-nociceptive (mechano-sensitive) information to the central nervous system.

Evaluation of cardiovascular risk-lowering health benefits accruing from laboratory-based, community-based and exercise-referral exercise programmes.

BACKGROUND: To evaluate the ability of community-based exercise programmes to facilitate public participation in exercise and hence improved cardiovascular health, we assessed the respective impacts of: a continuously monitored exercise programme based within our university (study 1); a Valleys Regional Park-facilitated community-based outdoor exercise programme (study 2); a Wales National Exercise Referral Scheme-delivered exercise-referral programme (study 3). METHODS: Biomolecular (monocytic PPARγ target gene expression), vascular haemodynamic (central/peripheral blood pressure, arterial stiffness), clinical (insulin sensitivity, blood lipids) and anthropometric (body mass index, waist circumference, heart rate) parameters were investigated using RT-PCR, applanation tonometry, chemical analysis and standard anthropometric techniques. RESULTS: In studies 1-3, 22/28, 32/65 and 11/14 participants adhered to their respective exercise programmes, and underwent significant increases in physical activity levels. Importantly, beneficial effects similar to those seen in our previous studies (eg, modulations in expression of monocytic PPARγ target genes, decreases in blood pressure/arterial stiffness, improvements in blood lipids/insulin sensitivity) were observed (albeit to slightly differing extents) only in participants who adhered to their respective exercise programmes. While study 1 achieved more intense exercise and more pronounced beneficial effects, significant cardiovascular risk-lowering health benefits related to biomolecular markers, blood pressure, arterial stiffness and blood lipids were achieved via community/referral-based delivery modes in studies 2 and 3. CONCLUSIONS: Because cardiovascular health benefits were observed in all 3 studies, we conclude that the majority of benefits previously reported in laboratory-based studies can also be achieved in community-based/exercise-referral settings. These findings may be of use in guiding policymakers with regard to introduction and/or continued implementation of community/referral-based exercise programmes.

Rate of involuntary admission in Dublin South West: a 5-year retrospective review.

OBJECTIVE: International figures for involuntary admissions vary widely. Differences in legislation, professionals' ethics and public attitudes towards risk have been known to influence this rate. Comparing involuntary admission rates in different parts of the same country can help control for variability found between international studies. This study assessed the rates of involuntary admissions in the Dublin South West Mental Health Service compared with the rest of Ireland. METHODS: We examined the demographic and clinical profiles of all involuntary patients admitted to the acute psychiatric inpatient unit in Tallaght Hospital between 2007 and 2011. We compared the rate of admission in Tallaght with the rest of Ireland. Data gathered included all patients detained on Form 6 and Form 13 (change of status) looking at age, gender, diagnosis and number of patients who had a Mental Health Tribunal. Form 7 (renewal orders) was also examined We calculated the rate per 100 000 population per year of Form 6 admissions, Form 13 and Form 7 (certificate and renewal order by responsible consultant psychiatrist) using figures from the 2006 Census. All data were analysed using SPSS. RESULTS: The rate of involuntary admission in Tallaght Hospital was significantly lower compared with the rest of Ireland (Form 6: t=-11.2; p<0.001, Form 13: t=-3.1; p=0.04, Form 7: t=-13.9; p=0.001). This difference was evident for all methods of involuntary detention and was also the case for Form 7 (renewal orders). Mental Health Tribunals were held for 59% of patients, a rate comparable with earlier findings described in publications, following the introduction of the new Mental Health Act. CONCLUSIONS: Rates per 100 000 population were lower in Dublin South West compared with the rest of Ireland. The reasons for this are not clear. Further research comparing similar services in Ireland could explain these findings.

Outcome after repair of tetralogy of Fallot with absent pulmonary valve.

BACKGROUND: Tetralogy of Fallot with absent pulmonary valve (TOF/APV) is associated with pulmonary artery dilatation and airway compression. METHODS: Since January 1, 1984, 28 patients with TOF/ APV have undergone complete repair (median age 11 days, range 1 day to 16 years). RESULTS: Thirteen patients were ventilated for respiratory failure preoperatively and extracorporeal membrane oxygenation was used in 3. Twenty-six patients underwent pulmonary artery plication (11 anterior, 15 anterior/ posterior). The right ventricular outflow tract (RVOT) was reconstructed with a patch (19), valved conduit (5), or monocusp valve (4). Early mortality was 21.4% (6/28), with 1 late death. All early deaths occurred in infants intubated preoperatively. Survival was 77% (95% confidence limit [CL] 56%, 89%) at 1 year and 72% (95% CL 50%, 86%) at 10 years. After surgery, 3 patients underwent reoperation for persistent respiratory symptoms, which resolved after repeat plication and placement of a valved conduit. Freedom from death or reoperation was 68% (95% CL 46%, 83%) at 1 year and 52% (95% CL 29%, 71%) at 10 years. In a multivariable analysis, only preoperative intubation was associated with a worse outcome (p = 0.04). CONCLUSIONS: Long-term outcome for patients with TOF/APV who survive the initial repair is good. Repeat plication and pulmonary valve implantation may improve outcome in patients with persistent airway compression.

National survey of MRSA: Ireland, 1995.

The objective of this survey was to obtain an indication of the size of the methicillin-resistant Staphylococcus aureus (MRSA) problem in Ireland prior to introducing national MRSA control guidelines. A survey of all microbiology laboratories in Ireland was carried out over two weeks in Spring 1995. For patients from whom MRSA was isolated during the study period standard demographic and clinical data were requested and period prevalence/1000 discharges was calculated. All 45 microbiology laboratories surveyed responded. MRSA was isolated from 448 patients during the two-week period. The period prevalence of MRSA was 16.5/1000 discharges. Males aged > or = 65 had the highest rate (50/1000 discharges). Half of all isolates were from patients in surgical or medical wards, but 4% were from community-based sources such as GPs, nursing homes and hospices. Thirty-two percent of MRSA patients were infected rather than colonized. MRSA is clearly a significant problem in Ireland. While it is largely a hospital problem at present, the increasing trend towards day procedures and shorter hospital stay means that infection will increase in the community.

Control and the prevention of methicillin-resistant Staphylococcus aureus in hospitals in Ireland: North/South Study of MRSA in Ireland 1999.

As part of an all-island survey of methicillin-resistant Staphylococcus aureus (MRSA) in the Republic of Ireland (the South), where there is a mixed public and private healthcare system, and Northern Ireland (the North), where the healthcare system is part of the UK National Health Service, a questionnaire was circulated to all participating hospitals on measures routinely taken to control MRSA. Response rates were 100% in the North and 89% in the South. Over 70% of hospitals screened particular groups of patients on admission to hospital. Ninety-five percent of hospitals in the North and 88% in the South attempted to eradicate MRSA from carriage sites. Most hospitals attempted to isolate or cohort positive patients. About a quarter of hospitals in both parts of Ireland screened new healthcare workers for the presence of MRSA. Terminal decontamination of the environment after the discharge of a patient positive for MRSA was the norm in over 90% of hospitals, however, 6% of hospitals in the South used inappropriate disinfectants for MRSA. All hospitals in the North, but a minority (41%) in the South, had written antibiotic prescribing policies, but only 65% of hospitals in the South had access to an infection control committee, acute hospitals having greater access than district hospitals. The prevention and control of spread of MRSA remains a major challenge in the North and in the South. Although most hospitals in the North and in the South implemented current recommended guidelines on the control of MRSA in hospitals, there was some variability that may be resource related. Policies need to be reviewed in the light of the changing epidemiology of MRSA.

Safety considerations and safety protocol for laser surgery.

The critical importance of laser safety depends on a precise knowledge of the physics of each type of laser and on the tissue effects each type produces in the constantly changing environment during surgery. The considerations involved in using the most common lasers--safety guidelines, general protocol, and specific measures--are outlined.

Evolving myocardial infarction during percutaneous transluminal coronary angioplasty: the use of portable percutaneous cardiopulmonary support.

Percutaneous transluminal coronary angioplasty (PTCA) has become an invaluable tool in the treatment of coronary artery disease. However, it is not without risks. For the PTCA patient who develops signs and symptoms of an evolving myocardial infarction, the time delay involved in the transportation of the patient from the angiography suite to the operating room becomes important. Institution of cardiopulmonary bypass in the angiography suite has enabled the successful transport of the patient to the operating room in a hemodynamically stable condition. We now present two case reports of patients treated with emergent percutaneous cardiopulmonary bypass following the development of myocardial infarction during PTCA.

The effect of sea transport from Ireland to the Lebanon on inflammatory, adrenocortical, metabolic and behavioural responses of bulls.

The objective was to investigate the effect of sea transport on the physiological, behavioural and performance responses of bulls. One-hundred and eleven bulls (mean body weight (standard error of the mean) 429 (5.7 kg)) were randomly assigned to one of three treatments; control (C; n=54) bulls were housed in 6 pens at Teagasc, Grange Research Centre at a stocking density of (1), 1.7 m(2)/head (C1.7; 3 pens) and (2), 3.4 m(2)/head (C3.4; 3 pens) and (3), transported (T) bulls (n=57) were penned at a space allowance of 1.7 m(2)/head (6 pens) and allocated to one of five decks on the shipping vessel. C and T bulls were subjected to the same live weight (d -2), blood sampling and rectal temperature (d -1) measurements pre-transport and on d 3, d 6, d 9 and d 11 of the study. T bulls had greater (P<0.05) live weight gain (+4.4%) compared with C1.7 bulls (-2.0%) and C3.4 (+0.13%)). Time spent lying was greater (P<0.05) among C1.7 and C3.4 bulls (9.9% and 53.3%, respectively) compared with T bulls (45.8%). Rectal body temperature was not different (P>0.05) among treatment groups throughout the study. At d 11, neutrophil % was greater (P<0.05) in transported bulls on decks 1, 2, 4 and 5 compared with C1.7 and C3.4 treatments. Plasma cortisol concentrations were not different (P>0.05) between control and transported bulls. Plasma creatine kinase (CK) activity was lower (P<0.05) among C3.4 and T bulls on decks 2, 3, 4 and 5 compared with d 3 values. In conclusion, the welfare of bulls transported by sea on the sea journey was not adversely affected. Housing control bulls at a reduced space allowance (1.7 m(2)) had a negative effect on live weight gain.

Contribution of nitric oxide to the blood pressure and arterial responses to exercise in humans.

An exaggerated blood pressure (BP) response to exercise predicts future cardiovascular risk. The mechanisms underlying exercise-induced hypertension remain unclear, although endothelial dysfunction and elevated arterial stiffness may contribute. Given the association between reductions in nitric oxide (NO) and vascular dysfunction, we sought to determine whether acute inhibition of NO synthase with N(G)-monomethyl-L-arginine (L-NMMA) would lead to exaggerated BP responses to maximal exercise and attenuate exercise-induced reductions in arterial stiffness. In 10 healthy subjects (31±5 years), BP and heart rate (HR) were measured before, during and after an incremental cycling exercise test to determine maximal oxygen consumption (VO(2)max). Trials were performed with placebo (saline) or intravenous infusion of L-NMMA on separate days in a randomized, double-blind, crossover design. Central (aortic) and peripheral (femoral) arterial stiffness were assessed using pulse wave velocity (PWV). BP was increased with L-NMMA at rest and during sub-maximal exercise, but not at maximal exercise (mean BP 117±5 vs 118±8 mm Hg, saline vs L-NMMA, P>0.05). Furthermore, L-NMMA had no influence on exercising HR or VO(2)max (P<0.05). Notably, aortic PWV was similarly increased after exercise with either saline or L-NMMA (P<0.05), whereas postexercise decreases in femoral PWV were attenuated with L-NMMA (P<0.05). Our findings suggest that NO is an important contributor to reductions in femoral artery stiffness after maximal exercise in healthy individuals. Furthermore, acute pharmacological inhibition of NO synthase causes augmented BP responses to sub-maximal exercise, but does not lead to exaggerated BP responses to maximal exercise or reduce maximal oxygen consumption.

BCP crystals increase prostacyclin production and upregulate the prostacyclin receptor in OA synovial fibroblasts: potential effects on mPGES1 and MMP-13.

OBJECTIVE: To investigate the potential involvement of prostacyclin in basic calcium phosphate (BCP) crystal-induced responses in osteoarthritic synovial fibroblasts (OASF). METHODS: OASF grown in culture were stimulated with BCP crystals. Prostacyclin production was measured by enzyme immunoassay. Expression of messenger RNA (mRNA) transcripts was assessed by real-time polymerase chain reaction (PCR). Expression of prostacyclin synthase (PGIS) and the prostacyclin (IP) receptor was measured. The effects of iloprost, a prostacyclin analogue, on expression of genes implicated in osteoarthritis such as microsomal prostaglandin E2 synthase 1 (mPGES1) and matrix metalloproteinases (MMPs) were also studied. FPT inhibitor II, a farnesyl transferase inhibitor, was used to antagonize iloprost-induced responses. RESULTS: BCP crystal stimulation led to a five-fold increase in prostacyclin production in OASF compared to untreated cells. This induction was attenuated by cyclooxygenase (COX)-2 and COX-1 inhibition at 4 and 32h, respectively. PGIS and IP receptor transcripts were constitutively expressed in OASF. BCP crystals upregulated IP receptor expression two-fold. While iloprost diminished BCP crystal-stimulated IP receptor upregulation, the inhibitory effect of iloprost was blocked by the farnesyl transferase inhibitor. In addition, iloprost upregulated mPGES1 and downregulated MMP-13 expression in BCP crystal-stimulated OASF, effects that were not influenced by the farnesyl transferase inhibitor. CONCLUSIONS: These data showed for the first time that BCP crystals can increase prostacyclin production and upregulate expression of the IP receptor in OASF. The potential of prostacyclin to influence BCP crystal-stimulated responses was supported by the effects of iloprost on the expression of the IP receptor, mPGES1 and MMP-13. These data demonstrate the potential involvement of prostacyclin in BCP crystal-associated osteoarthritis (OA) and suggest that inhibition of PG synthesis with non-steroidal anti-inflammatory drugs may have both deleterious and beneficial effects in BCP crystal-associated OA.

Is arterial stiffening in Alström syndrome linked to the development of cardiomyopathy?

BACKGROUND: Alström syndrome (AS) is a rare autosomal recessive condition characterized by retinal degeneration, childhood obesity, and severe insulin resistance. Dilated cardiomyopathy of unknown aetiology is a well-recognized and potentially lethal complication. The aim of this study was to investigate the relationship between vascular function, hyperinsulinaemia and cardiac performance in AS. MATERIALS AND METHODS: Fifteen subjects with AS (mean age 21 years, range 10-35) were studied and compared with age-, sex-, and blood pressure-matched healthy controls. Large artery stiffness and wave reflections were assessed in both groups by measuring aortic and brachial pulse wave velocity (PWV) (carotid-femoral and carotid-radial) and augmentation index (AIX) (Sphygmocor). In AS subjects, left ventricular function was assessed by echocardiography and metabolic parameters including fasting insulin, glucose, lipids and brain natriuretic peptide were also measured. RESULTS: Comparing AS subjects vs. controls (mean +/- SD), AIX was elevated in AS subjects (18 +/- 9% vs. 3 +/- 11%, P < 0.0001). No significant changes in brachial PWV (8.1 +/- 1.3 m s(-1) vs. 7.3 +/- 1.1 m s(-1), P = 0.14) or aortic PWV (6.5 +/- 1.1 m s(-1) vs. 6.0 +/- 1.0 m s(-1), P = 0.26) were observed. AS subjects were hyperinsulinaemic and had disturbances in lipid profiles relative to controls. No correlations were observed between vascular, metabolic and echocardiographic parameters. CONCLUSIONS: In AS there are alterations in the shape of the central arterial pressure waveform associated with augmented aortic systolic pressure and indicative of increased wave reflection. Unfavourable central arterial haemodynamics in AS may contribute to the development of cardiomyopathy but other aetiological factors are probably involved.