Endothelial Surface Layer Degradation by Chronic Hyaluronidase Infusion Induces Proteinuria in Apolipoprotein E-Deficient Mice

Functional studies show that disruption of endothelial surface layer (ESL) is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for vascular dysfunction remains to be demonstrated. We examined if loss of ESL through enzymatic degradation would affect vascular barrier properties in an atherogenic model. Eight week old male apolipoprotein E deficient mice on Western-type diet for 10 weeks received continuous active or heat-inactivated hyaluronidase (10 U/hr, i.v.) through an osmotic minipump during 4 weeks. Blood chemistry and anatomic changes in both macrovasculature and kidneys were examined. Infusion with active hyaluronidase resulted in decreased ESL (0.32±0.22 mL) and plasma volume (1.03±0.18 mL) compared to inactivated hyaluronidase (0.52±0.29 mL and 1.28±0.08 mL, p<0.05 respectively).Active hyaluronidase increased proteinuria compared to inactive hyaluronidase (0.27±0.02 vs. 0.15±0.01 µg/µg protein/creatinin, p<0.05) without changes in glomerular morphology or development of tubulo-interstitial inflammation. Atherosclerotic lesions in the aortic branches showed increased matrix production (collagen, 32±5 vs. 18±3%; glycosaminoglycans, 11±5 vs. 0.1±0.01%, active vs. inactive hyaluronidase, p<0.05). ESL degradation in apoE deficient mice contributes to reduced increased urinary protein excretion without significant changes in renal morphology. Second, the induction of compositional changes in atherogenic plaques by hyaluronidase point towards increased plaque vulnerability. These findings support further efforts to evaluate whether ESL restoration is a valuable target to prevent (micro) vascular disease progressio

Pregnancy related anxiety and general anxious or depressed mood and the choice for birth setting:A secondary data-analysis of the DELIVER study

BACKGROUND: In several developed countries women with a low risk of complications during pregnancy and childbirth can make choices regarding place of birth. In the Netherlands, these women receive midwife-led care and can choose between a home or hospital birth. The declining rate of midwife-led home births alongside the recent debate on safety of home births in the Netherlands, however, suggest an association of choice of birth place with psychological factors related to safety and risk perception. In this study associations of pregnancy related anxiety and general anxious or depressed mood with (changes in) planned place of birth were explored in low risk women in midwife-led care until the start of labour. METHODS: Data (n = 2854 low risk women in midwife-led care at the onset of labour) were selected from the prospective multicenter DELIVER study. Women completed the Pregnancy Related Anxiety Questionnaire-Revised (PRAQ-R) to assess pregnancy related anxiety and the EuroQol-6D (EQ-6D) for an anxious and/or depressed mood. RESULTS: A high PRAQ-R score was associated with planned hospital birth in nulliparous (aOR 1.92; 95% CI 1.32–2.81) and parous women (aOR 2.08; 95% CI 1.55–2.80). An anxious or depressed mood was associated with planned hospital birth (aOR 1.58; 95% CI 1.20–2.08) and with being undecided (aOR 1.99; 95% CI 1.23–2.99) in parous women only. The majority of women did not change their planned place of birth. Changing from an initially planned home birth to a hospital birth later in pregnancy was, however, associated with becoming anxious or depressed after 35 weeks gestation in nulliparous women (aOR 4.17; 95% CI 1.35–12.89) and with pregnancy related anxiety at 20 weeks gestation in parous women (aOR 3.91; 95% CI 1.32–11.61). CONCLUSION: Low risk women who planned hospital birth (or who were undecided) more often reported pregnancy related anxiety or an anxious or depressed mood. Women who changed from home to hospital birth during pregnancy more often reported pregnancy related anxiety or an anxious or depressed mood in late pregnancy. Anxiety should be adequately addressed in the process of informed decision-making regarding planned place of birth in low risk women

Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus

Endothelial glycocalyx perturbation contributes to increased vascular permeability. In the present study we set out to evaluate whether: (1) glycocalyx is perturbed in individuals with type 2 diabetes mellitus, and (2) oral glycocalyx precursor treatment improves glycocalyx properties. Male participants with type 2 diabetes (n = 10) and controls (n = 10) were evaluated before and after 2 months of sulodexide administration (200 mg/day). The glycocalyx dimension was estimated in two different vascular beds using sidestream dark field imaging and combined fluorescein/indocyanine green angiography for sublingual and retinal vessels, respectively. Transcapillary escape rate of albumin (TER(alb)) and hyaluronan catabolism were assessed as measures of vascular permeability. Both sublingual dimensions (0.64 [0.57-0.75] μm vs 0.78 [0.71-0.85] μm, p <0.05, medians [interquartile range]) and retinal glycocalyx dimensions (5.38 [4.88-6.59] μm vs 8.89 [4.74-11.84] μm, p <0.05) were reduced in the type 2 diabetes group compared with the controls whereas TER(alb) was increased (5.6 ± 2.3% vs 3.7 ± 1.7% in the controls, p <0.05). In line with these findings, markers of hyaluronan catabolism were increased with diabetes (hyaluronan 137 ± 29 vs 81 ± 8 ng/ml and hyaluronidase 78 ± 4 vs 67 ± 2 U/ml, both p <0.05). Sulodexide increased both the sublingual and retinal glycocalyx dimensions in participants with diabetes (to 0.93 [0.83-0.99] μm and to 5.88 [5.33-6.26] μm, respectively, p <0.05). In line, a trend towards TER(alb) normalisation (to 4.0 ± 2.3%) and decreases in plasma hyaluronidase (to 72 ± 2 U/ml, p <0.05) were observed in the diabetes group. Type 2 diabetes is associated with glycocalyx perturbation and increased vascular permeability, which are partially restored following sulodexide administration. Further studies are warranted to determine whether long-term treatment with sulodexide has a beneficial effect on cardiovascular risk. www.trialregister.nl NTR780/ http://isrctn.org ISRCTN82695186 An unrestricted Novartis Foundation for Cardiovascular Excellence grant (2006) to M. Nieuwdorp/E. S. G. Stroes, Dutch Heart Foundation (grant number 2005T037

Impaction bone grafting of the acetabulum at hip revision using a mix of bone chips and a biphasic porous ceramic bone graft substitute: Good outcome in 43 patients followed for a mean of 2 years

Background and purpose One of the greatest problems of revision hip arthroplasty is dealing with lost bone stock. Good results have been obtained with impaction grafting of allograft bone. However, there have been problems of infection, reproducibility, antigenicity, stability, availability of bone, and cost. Thus, alternatives to allograft have been sought. BoneSave is a biphasic porous ceramic specifically designed for use in impaction grafting. BoneSave is 80% tricalcium phosphate and 20% hydroxyapatite. Previous in vitro and in vivo studies have yielded good results using mixtures of allograft and BoneSave, when compared with allograft alone. This study is the first reported human clinical trial of BoneSave in impaction grafting

Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study

<p>Abstract</p> <p>Background</p> <p>The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality.</p> <p>Methods/Design</p> <p>We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥10⁵ colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥10⁵ CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs.</p> <p>Discussion</p> <p>This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16–22 weeks of pregnancy and subsequent nitrofurantoin treatment.</p> <p>Trial registration</p> <p>Dutch trial registry: NTR-3068</p