The effects of metformin on maternal haemodynamics in gestational diabetes mellitus: A pilot study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major clinical challenge and is likely to remain so as the incidence of GDM continues to increase AIM: To assess longitudinal changes in maternal haemodynamics amongst women diagnosed with GDM requiring either metformin or dietary intervention in comparison to low-risk healthy controls. METHODOLOGY: Fifty-six pregnant women attending their first appointment at the GDM clinic and 60 low-risk healthy pregnant controls attending their routine antenatal clinics were recruited and assigned to three groups: GDM Metformin (GDM-M), GDM Diet (GDM-D) and Control. Non-invasive assessment of maternal haemodynamics, using recognised measures of arterial stiffness and central blood pressure (Arteriograph®), were undertaken under controlled conditions within four gestational windows: antenatal; AN1 (26-28 weeks), AN2 (32-34 weeks) and AN3 (37-40 weeks), and postnatal (PN) (6-8 weeks after delivery). Data were analysed using a linear mixed model incorporating gestational age and other relevant predictors, including age, blood pressure (BP), baseline bodyweight and pulse as fixed effects, and patient as a random effect. RESULTS: Fitted linear mixed models showed evidence of a two-way interaction effect between groups (GDM-D, GDM-M and Control) and stages of gestation (AN1, AN2, AN3 and PN) for maternal haemodynamic parameters: brachial artery augmentation index (AIx) (p=0.004), aortic AIx (p=0.008), and central systolic BP (p=0.001). However, differences in respect of aortic pulse wave velocity (p=0.001) and heart rate (p<0.001) were only significant for gestational stage. At AN2, we did not observe any evidence that the mean brachial Aix in the GDM-M was different from the control group (p=0.158). CONCLUSION: AIx and central systolic BP measures of arterial stiffness are adversely affected by GDM in comparison to controls during pregnancy. The possible beneficial effects of metformin therapy seen at 32 to 34 weeks of gestation require further exploration

Diurnal variation and repeatability of arterial stiffness and cardiac output measurements in the third trimester of uncomplicated pregnancy.

AIM: To investigate same day repeated measures and diurnal variation of arterial stiffness, cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) during the third trimester of normal pregnancy. METHODOLOGY: Pulse wave velocity (PWV) and augmentation index (AIx) were recorded using the Arteriograph, while CO, SV and TPR were recorded using noninvasive cardiac output monitoring. The measurements were obtained in the third trimester of pregnancy from 21 healthy pregnant women at four time points (morning, afternoon, evening and midnight) over a 24-h period. Triplicate measurements of 67 women were obtained at 5-min intervals to assess repeatability between measurements within a patient. RESULTS: Diurnal measurements of arterial stiffness for brachial AIx, aortic AIx and PWV were not statistically significantly different at any of the four time points. Estimated means (SD) for PWV at the four stated time points were 7.81 (2.05), 8.45 (1.68), 7.87 (1.74) and 7.64 m/s (1.15), respectively (P = 0.267). Estimates for AIx at those time points were 10.22 (15.62), 4.44 (10.07), 6.49 (10.92) and 8.40% (8.16), respectively (P = 0.295). Similarly, mean arterial pressure, SV, SV index and TPR did not show any evidence of diurnal variation. However, we observed that the mean CO, cardiac index (CI) and heart rate (HR) varied from morning to midnight; the mean CO, HR and CI increased significantly in the afternoon compared with the corresponding mean morning measurements in a similar fashion to HR. Mean (SD) CO estimates at the four stated time points were 5.90 (1.33), 6.38 (1.49), 6.18 (1.43) and 5.80 ml/min (1.19), respectively, (P < 0.001), whereas mean CI estimates were 3.65 (0.58), 3.93 (0.68), 3.81 (0.65), and 3.57 (0.48), respectively, (P < 0.001), and mean HR estimates were 95 (12), 98 (13), 95 (12) and 88 (12.98), respectively (P < 0.001). Triplicate measurements of 61 women in our repeatability study showed moderate-to-high correlation between observations on the same woman for all Arteriograph and noninvasive cardiac output monitoring variables (estimates of intraclass correlation ranged from 0.49 to 0.91). CONCLUSION: With the exception of CO, CI and HR which showed a diurnal variation, measurements of most haemodynamic parameters did not change significantly from morning to midnight, suggesting there was no evidence of systematic differences in the mean values of these variables at these time points. Multiple consecutive noninvasive measurements of vascular stiffness, CO, SV and TPR were highly correlated confirming repeatability of measurements in the third trimester of uncomplicated pregnancy, so these haemodynamic measurements do not need to be undertaken at a specific time period of the day

The conceptual and practical ethical dilemmas of using health discussion board posts as research data.

Increasing numbers of people living with a long-term health condition are putting personal health information online, including on discussion boards. Many discussion boards contain material of potential use to researchers; however, it is unclear how this information can and should be used by researchers. To date there has been no evaluation of the views of those individuals sharing health information online regarding the use of their shared information for research purposes

Antibacterial activity of extracts from Calophyllum canum

The species of the genus Calophyllum (Guttiferae) are mainly distributed in tropical area. Plants from this genus are known as a rich source of secondary metabolite such as xanthones, coumarins, chromenes, flavonoids and triterpenoids. Some of this compounds exhibit significant biological effects antibacterial, antifungal, anti HIV and immunomodulatory activities. Calophyllum canum or Betangur baatu is a forest tree that found in Penisular of Malaysia. The research is aimed to investigate the bioactivity of C. canum extracts against selected bacteria. The chemical constituent of the plant is also investigated. The extracts are tested for their activity to inhibit the growth of Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. The anti bacterial testing is carried out by disc diffusion method. It is concluded the C. canum has a greater potency to inhibit the growth of bacteria. The results of antibacterial of the extracts will be discussed in this paper

Does treatment modality affect measures of arterial stiffness in women with gestational diabetes?

OBJECTIVES: The incidence of gestational diabetes mellitus (GDM) is increasing and is associated with adverse maternal, fetal and neonatal outcomes. Arterial stiffness (AS) is raised in pregnancies complicated by placental-mediated diseases such as pre-eclampsia. We investigated if AS is different between healthy pregnancies and women with GDM on different treatment modalities. METHODS: We conducted a prospective longitudinal cohort study to assess and compare AS in pregnancies complicated by GDM with low-risk controls. AS, measured by pulse wave velocity (PWV) and brachial (BrAIx) and aortic (AoAIx) augmentation Index, was recorded using the Arteriograph® at four gestational windows: 24+0 to 27+6; 28+0 to 31+6; 32+0 to 35+6 and ≥36+0 weeks of gestation (windows W1-W4, respectively). Women with GDM were considered both as a single group, and as subgroups defined by treatment modality. Data were analyzed using a linear mixed model on each AS variable (log-transformed) with group, gestational windows, maternal age, ethnicity, parity, body mass index, mean arterial pressure and heart rate as fixed effects and individual as a random effect. We compared the group means including relevant contrasts and adjusted the p-values using the Bonferroni correction. RESULTS: The study population comprised 155 low-risk controls and 127 with GDM, of whom 59 were treated with dietary intervention, 47 with metformin alone and 21 with metformin plus insulin. The two-way interaction term of study group and gestational age was significant for BrAIx and AoAIx (p<0.001), though there was no evidence (p=0.729) that mean AoPWV was different between the study groups. Women in the control group demonstrated significantly lower BrAIx and AoAIX at gestational windows W1-3 compared to the combined GDM group, but not at W4. Mean (95% CI) difference in log adjusted BrAIx was -0.37 (-0.52, 0.22), -0.23 (-0.35, -0.12), and -0.29 (-0.40, -0.18) at W1, W2 and W3, respectively. Mean (95% CI) difference in log adjusted AoAIx was -0.49 (-0.69, -0.3), -0.32 (-0.47, -0.18) and -0.38 (-0.52, -0.24) at W1, W2 and W3, respectively. Similarly, women in the control group also demonstrated significantly lower BrAIx and AoAIx compared with each of the GDM treatment subgroups (diet, metformin and metformin plus insulin) at W1-3. The increase in mean BrAIx and AoAIx seen between W2 and W3 in the women with GDM treated with dietary management was attenuated in the metformin and metformin with insulin groups, however the mean differences in BrAIx and AoAIx between these treatment groups were not statistically significant at any gestational window. CONCLUSIONS: Pregnancies complicated by GDM demonstrate significantly higher AS compared to low-risk pregnancies regardless of treatment modality. Our data provides a basis for further investigation into the association of metformin therapy with changes in AS and risk of placental-mediated diseases. This article is protected by copyright. All rights reserved

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

Evaluation of inducible nitric oxide synthase inhibition on kidney function and structure in high-fat diet-induced kidney disease

peer reviewedBACKGROUND: Central obesity is related to caloric excess promoting deleterious cellular responses in targeted organs. Nitric oxide (NO) has been determined as a key player in the pathogenesis of metabolic diseases. Here, we investigated the implication of inducible NO synthase (iNOS) in the development of obesity-induced kidney disease. MATERIALS AND METHODS: C57Bl/6 male mice were randomized to a low-fat diet (LFD) or a high-fat diet (HFD) and treated with L-NIL, a specific iNOS inhibitor for 16 weeks. RESULTS: Mice fed a HFD exhibited a significant increase in body weight, fasting blood glucose, plasma levels of NEFA, triglyceride and insulin. iNOS inhibition prevented these changes in mice fed a HFD. Interestingly, the significant increase in albuminuria and mesangial matrix expansion were not ameliorated with L-NIL whereas a significant decrease in proteinuria, NAG (N-acetyl-ß-D-glucosaminidase) excretion and renal triglycerides content were found, suggesting that iNOS inhibition is more suitable for tubular function than glomerular function. The urinary hydrogen peroxide level, a stable product of ROS production, that was found to be increased in mice fed a HFD, was significantly reduced with L-NIL. Finally, despite a moderate effect of L-NIL on inflammatory process in the kidney, we demonstrated a positive impact of this treatment on adipocyte hypertrophy and on adipose tissue inflammation. CONCLUSIONS: These results suggest that inhibition of iNOS leads to a moderate beneficial effect on kidney function in mice fed a HFD. Further studies are needed for better understanding of the role of iNOS in obesity-induced kidney disease. This article is protected by copyright. All rights reserved

Measurement of the top quark mass using the matrix element technique in dilepton final states

We present a measurement of the top quark mass in pp¯ collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider. The data were collected by the D0 experiment corresponding to an integrated luminosity of 9.7  fb−1. The matrix element technique is applied to tt¯ events in the final state containing leptons (electrons or muons) with high transverse momenta and at least two jets. The calibration of the jet energy scale determined in the lepton+jets final state of tt¯ decays is applied to jet energies. This correction provides a substantial reduction in systematic uncertainties. We obtain a top quark mass of mt=173.93±1.84  GeV

Cerebrospinal fluid matrix metalloproteinase-9 increases during treatment of recurrent malignant gliomas

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinases (MMPs) are enzymes that promote tumor invasion and angiogenesis by enzymatically remodeling the extracellular matrix. MMP-2 and MMP-9 are the most abundant forms of MMPs in malignant gliomas, while a 130 kDa MMP is thought to be MMP-9 complexed to other proteinases. This study determined whether doxycycline can block MMP activity <it>in vitro</it>. We also measured MMP-2 and MMP-9 levels in cerebrospinal fluid (CSF) from patients with recurrent malignant gliomas.</p> <p>Methods</p> <p>To determine whether doxycycline can block MMP activity, we measured the extent of doxycyline-mediated MMP-2 and MMP-9 inhibition <it>in vitro </it>using epidermal growth factor receptor (EGFR) transfected U251 glioma cell lines. MMP activity was measured using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) zymography. In addition, patients underwent lumbar puncture for CSF sampling at baseline, after 6 weeks (1 cycle), and after 12 weeks (2 cycles), while being treated with a novel chemotherapy regimen of irinotecan, thalidomide, and doxycycline designed to block growth/proliferation, angiogenesis, and invasion. Irinotecan was given at 125 mg/m²/week for 4 weeks in 6-week cycles, together with continuous doxycycline at 100 mg twice daily on Day 1 and 50 mg twice daily thereafter. Daily thalidomide dose in our cohort was 400 mg. Tumor progression was monitored by magnetic resonance imaging (MRI).</p> <p>Results</p> <p>Doxycyline <it>in vitro </it>completely abolished MMP-9 activity at 500 μg/ml while there was only 30 to 50% inhibition of MMP-2 activity. Four patients respectively completed 4, 3, 1, and 2 cycles of irinotecan, thalidomide, and doxycycline. Patient enrollment was terminated after one patient developed radiologically defined pulmonary embolism, and another had probable pulmonary embolism. Although CSF MMP-2 and 130 kDa MMP levels were stable, MMP-9 level progressively increased during treatment despite stable MRI.</p> <p>Conclusion</p> <p>Doxycycline can block MMP-2 and MMP-9 activities from glioma cells <it>in vitro</it>. Increased CSF MMP-9 activity could be a biomarker of disease activity in patients with malignant gliomas, before any changes are detectable on MRI.</p

Mosquito Feeding Affects Larval Behaviour and Development in a Moth

Organisms are attacked by different natural enemies present in their habitat. While enemies such as parasitoids and predators will kill their hosts/preys when they successfully attack them, enemies such as micropredators will not entirely consume their prey. However, they can still have important consequences on the performance and ecology of the prey, such as reduced growth, increased emigration, disease transmission