| 11. |
- Proletov, Ian, et al.
(author)
-
Primary and secondary glomerulonephritides 1.
- 2014
-
In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
-
Journal article (peer-reviewed)
|
|
| 12. |
- Ayres-de-Campos, D., et al.
(author)
-
A randomised clinical trial of intrapartum fetal monitoring with computer analysis and alerts versus previously available monitoring
- 2010
-
In: BMC Pregnancy and Childbirth. - : BioMed Central Ltd.. - 1471-2393 .- 1471-2393. ; 10:71
-
Journal article (peer-reviewed)abstract
- Background: Intrapartum fetal hypoxia remains an important cause of death and permanent handicap and in a significant proportion of cases there is evidence of suboptimal care related to fetal surveillance. Cardiotocographic (CTG) monitoring remains the basis of intrapartum surveillance, but its interpretation by healthcare professionals lacks reproducibility and the technology has not been shown to improve clinically important outcomes. The addition of fetal electrocardiogram analysis has increased the potential to avoid adverse outcomes, but CTG interpretation remains its main weakness. A program for computerised analysis of intrapartum fetal signals, incorporating real-time alerts for healthcare professionals, has recently been developed. There is a need to determine whether this technology can result in better perinatal outcomes. Methods/design: This is a multicentre randomised clinical trial. Inclusion criteria are: women aged ≥ 16 years, able to provide written informed consent, singleton pregnancies ≥ 36 weeks, cephalic presentation, no known major fetal malformations, in labour but excluding active second stage, planned for continuous CTG monitoring, and no known contra-indication for vaginal delivery. Eligible women will be randomised using a computer-generated randomisation sequence to one of the two arms: continuous computer analysis of fetal monitoring signals with real-time alerts (intervention arm) or continuous CTG monitoring as previously performed (control arm). Electrocardiographic monitoring and fetal scalp blood sampling will be available in both arms. The primary outcome measure is the incidence of fetal metabolic acidosis (umbilical artery pH < 7.05, BDecf > 12 mmol/L). Secondary outcome measures are: caesarean section and instrumental vaginal delivery rates, use of fetal blood sampling, 5-minute Apgar score < 7, neonatal intensive care unit admission, moderate and severe neonatal encephalopathy with a marker of hypoxia, perinatal death, rate of internal monitoring, tracing quality, and signal loss. Analysis will follow an intention to treat principle. Incidences of primary and secondary outcomes will be compared between groups. Assuming a reduction in metabolic acidosis from 2.8% to 1.8%, using a two-sided test with alpha = 0.05, power = 0.80, and 10% loss to follow-up, 8133 women need to be randomised. Discussion: This study will provide evidence of the impact of intrapartum monitoring with computer analysis and real-time alerts on the incidence of adverse perinatal outcomes, intrapartum interventions and signal quality. (Current controlled trials ISRCTN42314164)
|
|
| 13. |
|
|
| 14. |
- Lopes, P. C., et al.
(author)
-
Cyclosporine A enhances gluconeogenesis while sirolimus impairs insulin signaling in peripheral tissues after 3 weeks of treatment
- 2014
-
In: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839. ; 91:1, s. 61-73
-
Journal article (peer-reviewed)abstract
- Cyclosporine A (CsA) and sirolimus (SRL) are immunosuppressive agents (IA) associated with new-onset diabetes after transplantation (NODAT). This study aims to evaluate the effects of 3-weeks of treatment with either CsA (5 mg/kg BW/day) or SRL (1 mg/kg BW/day) on insulin signaling and expression of markers involved in glucose metabolism in insulin-sensitive tissues, in Wistar rats. Although no differences were observed in fasting glucose, insulin or C-peptide levels, both treated groups displayed an impaired glucose excursion during both glucose and insulin tolerance tests. These results suggest glucose intolerance and insulin resistance. An increase in glucose-6-phosphatase protein levels (68%, p<0.05) and in protein-tyrosine phosphatase 1B (163%,p<0.05), a negative regulator of insulin was observed in the CsA-treated group in the liver, indicating enhanced gluconeogenesis and increased insulin resistance. On the other hand, glucokinase protein levels were decreased in the SRL group (35%, p < 0.05) compared to vehicle, suggesting a decrease in glucose disposal. SRI treatment also reduced peroxisome proliferator-activated receptor gamma coactivator 1 alpha protein expression in muscle (similar to 50%, p<0.05), while no further protein alterations were observed in muscle and perirenal adipose tissue nor with the CsA treatment. Moreover, the phosphorylation of key proteins of the insulin signaling cascade was suppressed in the SRL group, but was unchanged by the CsA treatment. Taken together, these data suggest that CsA treatment enhances gluconeogenic factors in liver, while SRL treatment impairs insulin signaling in peripheral tissues, which can contribute to the development of insulin resistance and NODAT associated with immunosuppressive therapy.
|
|
| 15. |
- Eardley, S., et al.
(author)
-
A pilot feasibility study of a questionnaire to determine European union-wide CAM use
- 2012
-
In: Forschende Komplementarmedizin. - : S. Karger AG. - 1661-4119. ; 19:6, s. 302-310
-
Journal article (peer-reviewed)abstract
- Background: No questionnaire specifically measuring the core components of complementary and alternative medicine (CAM) use has been validated for use across European Union (EU) countries. We aimed to determine the face validity, acceptability and the participants' comprehension of a pre-existing questionnaire designed to measure 'CAM use', to provide a comparative, standardised questionnaire for use by health care providers, policy makers and purchasers throughout Europe. Methods: Established procedures were employed to translate the questionnaire into 4 EU languages. The translated questionnaires were piloted on 50 healthy adults from each country who may never have used CAM. 10 participants per country also took part in audio-recorded think aloud interviews about the questionnaire. The interviews were transcribed and analysed in the language in which they were conducted; findings were summarised in English. Questionnaire data were pooled across countries, and patterns of completion and missing data were analysed. Results: The questionnaire was translated into Italian, Spanish, Dutch and Romanian. The mean age of the participants was 43.6 years. 34% were male, 87.4% were either light or heavy CAM users, and 12.6% were non-users. Qualitative analysis identified common problems across countries including a 'hard-to-read' layout, misunderstood terminology and uncertainty in choosing response options. Quantitative analysis confirmed that a substantial minority of respondents failed to follow questionnaire instructions and that some questions had substantial rates of missing data. Conclusions: The I-CAM-Q has low face validity and low acceptability, and is likely to produce biased estimates of CAM use if applied in England, Romania, Italy, The Netherlands or Spain. Further work is required to develop the layout, terms, some response options and instructions for completion before it can be used across the EU. © 2012 S. Karger AG, Basel.
|
|
| 16. |
- Leite, Liz M., et al.
(author)
-
Anti-inflammatory Properties of Doxycycline and Minocycline in Experimental Models : An in Vivo and in Vitro Comparative Study
- 2011
-
In: InflammoPharmacology. - : Springer. - 0925-4692 .- 1568-5608. ; 19:2, s. 99-110
-
Journal article (peer-reviewed)abstract
- Aims and methods: Minocycline (Mino) and doxycycline (Dox) are second generation tetracyclines known to present several other effects, which are independent from their antimicrobial activities. We studied in a comparative way the anti-inflammatory effects of Mino and Dox, on acute models of peripheral inflammation in rodents (formalin test and peritonitis in mice, and carrageenan-induced paw oedema in rats). Immunohistochemical assays for TNF-alpha and iNOS in rat paws of carrageenan-induced oedema were also carried out as well as in vitro assays for myeloperoxidase (MPO) and lactate dehydrogenase (LDH). Furthermore, antioxidant activities were evaluated by the DPPH assay. Results: In the formalin test although Mino and Dox (1, 5, 10 and 25 mg/kg, i.p.) inhibited the first phase, they acted predominantly on the second phase of the test, where inhibition of the licking time close to 80% were observed. Mino and Dox were very efficacious in reducing the carrageenan-induced paw oedema in rats (10, 25 and 50 mg/kg, i.p.) and carrageenan-induced leucocyte migration (1 and 5 mg/kg, i.p.) to mice peritoneal cavities. Besides, they also significantly inhibited MPO and LDH releases at doses ranging from 0.001 to 1 μg/ml. Thus, in general, the anti-inflammatory activity of Dox was higher as compared to that of Mino, although the radical scavenging activity of Mino was of a magnitude 10 times higher. Conclusions: Our data indicate that anti-inflammatory and antioxidant effects, involve the inhibition of iNOS and TNF-alpha, among other properties, and these encourage clinical studies of these compounds for new therapeutic applications, especially those were inflammation plays a role.
|
|
| 17. |
- Lincoff, A. Michael, et al.
(author)
-
Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial
- 2014
-
In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 35:37, s. 2516-2523
-
Journal article (peer-reviewed)abstract
- Aims Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). Methods and results A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50,150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for similar to 2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. Conclusions Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.
|
|
| 18. |
- Lobo, Andrea C., et al.
(author)
-
Cleavage of the vesicular glutamate transporters under excitotoxic conditions
- 2011
-
In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 44:3, s. 292-303
-
Journal article (peer-reviewed)abstract
- Glutamate is loaded into synaptic vesicles by vesicular glutamate transporters (VGLUTs), and alterations in the transporters expression directly regulate neurotransmitter release. We investigated changes in VGLUT1 and VGLUT2 protein levels after ischemic and excitotoxic insults. The results show that VGLUT2 is cleaved by calpains after excitotoxic stimulation of hippocampal neurons with glutamate, whereas VGLUT1 is downregulated to a lower extent VGLUT2 was also cleaved by calpains after oxygen/glucose deprivation (OGD), and downregulated after middle cerebral artery occlusion (MCAO) and intrahippocampal injection of kainate. In contrast, VGLUT1 was not affected after OGD. Incubation of isolated synaptic vesicles with recombinant calpain also induced VGLUT2 cleavage, with a little effect observed for VGLUT1. N-terminal sequencing analysis showed that calpain cleaves VGLUT2 in the C-terminus, at Asn(534) and Lys(542). The truncated GFP-VGWT2 forms were found to a great extent in non-synaptic regions along neurites, when compared to GFP-VGLUT2. These findings show that excitotoxic and ischemic insults downregulate VGLUT2, which is likely to affect glutamatergic transmission and cell death, especially in the neonatal period when the transporter is expressed at higher levels. (C) 2011 Elsevier Inc. All rights reserved.
|
|
| 19. |
- Mancera-Romero, J., et al.
(author)
-
Fasting apolipoprotein B48 is a marker for peripheral arterial disease in type 2 diabetes
- 2013
-
In: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 50:3, s. 383-389
-
Journal article (peer-reviewed)abstract
- An earlier study showed that fasting and postprandial concentrations of apolipoprotein B48 were raised in patients with type 2 diabetes (DM2) and peripheral arterial disease (PAD) as compared with persons without DM2 or persons with DM2 but not PAD. The aim of this study was to confirm the association of PAD and B48 in a larger group of patients with DM2 and the relation of B48 with the preheparin lipoprotein lipase (LPL) mass. We studied 456 patients with DM2. PAD was defined as an ankle-brachial index (ABI) < 0.9. Apolipoprotein B48 was quantified by ELISA. Apo B48 was significantly higher in the group with an ABI < 0.9 than the groups with ABI of 0.9-1.3 and > 1.3 (10.7 +/- A 6.28 vs. 9.24 +/- A 5.5 vs. 9.17 +/- A 8.8 mg/L, ANOVA test, p < 0.05). B48 was independently associated with an ABI < 0.9 (OR 1.053; 95 % CI, 1.013-1.094; p < 0.05), together with smoking and duration of diabetes. The preheparin LPL mass was similar in the patients with and without PAD. In conclusion, we confirmed that fasting B48 is an independent marker of PAD in patients with DM2, unrelated to the preheparin LPL mass, statin therapy or glucose lowering treatment.
|
|
| 20. |
|
|
