Vascular Dysfunction in Horses with Endocrinopathic Laminitis

Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein) and the facial skin (facial skin arteries) by small vessel wire myography. The response to vasoconstrictors phenylephrine (10-9-10-5M) and 5-hydroxytryptamine (5HT; 10-9-10-5M) and the vasodilator acetylcholine (10-9-10-5M) was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 ± 94.1% v EL 90.8 ± 4.4%, P = 0.01, laminar veins 129.4 ± 14.8% v EL 71.2 ± 4.1%, P = 0.005 and facial skin arteries 182.0 ± 40.7% v EL 91.4 ± 4.5%, P = 0.01). In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006) and veins (P = 0.009) from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof

Microscopic hematuria in pregnancy: Relevance to pregnancy outcome

Background: The significance of dipstick or microscopic hematuria in pregnancy is uncertain, with some studies suggesting this is associated with a greater risk for preeclampsia. We sought to determine the prevalence and clinical significance of microscopic hematuria during pregnancy. Methods: This was a prospective case-control study in the antenatal Clinic of St George Hospital, Kogarah, Australia, a teaching hospital without tertiary referral antenatal care, with approximately 2,600 deliveries per year. One thousand pregnant women attending for routine antenatal care were invited to have a routine urinalysis performed and be referred to a nephrology clinic for further investigation if dipstick microscopic hematuria was detected on more than 1 occasion before 32 weeks' gestation. Main outcome measures were the prevalence of dipstick hematuria, prevalence of hematuria confirmed by urine microscopy, and the development of preeclampsia or gestational hypertension or delivery of a small-for-gestational-age baby. Results: One hundred seventy-eight of 902 women (20%) who entered the study had dipstick hematuria on at least 2 occasions in pregnancy; 66 of 126 women (53%) who had hematuria before 32 weeks attended the nephrology clinic, where microscopic hematuria was confirmed in 40 women (61%). Renal imaging results were normal in all except 1 woman, and all women had a serum creatinine level of 0.90 mg/dL or less (≤80 μmol/L). The development of preeclampsia or gestational hypertension or delivery of a small-for-gestational-age baby were similar in women with and without dipstick hematuria. Microscopic hematuria persisted in half (15 women) of those who attended for follow-up after 3 months postpartum. Conclusion: Dipstick hematuria is very common during pregnancy, but rarely signifies a disorder likely to impact on the pregnancy outcome. Postpartum follow-up is recommended to detect women who have persistent hematuria and presumed underlying mild glomerulonephritis. © 2005 by the National Kidney Foundation, Inc

The effect of mannitol on renal function following cardio-pulmonary bypass in patients with normal pre-operative creatinine

Mannitol is often added to the cardiopulmonary bypass pump prime to reduce the incidence of renal dysfunction, but studies so far have been inconclusive. Urinary excretion of microalbumin and retinol binding protein are more sensitive than routine biochemical tests of renal function after cardiac surgery. We performed a double-blind, randomised, controlled trial in cardiac surgical patients with pre-operative plasma creatinine < 130 mu mol.l(-1). Twenty patients received 0.5 g.kg(-1) of mannitol in the pump prime, whereas 20 control patients received an equivalent volume of Hartmann's solution. Blood and urine samples were taken on the day before surgery and daily for 5 days postoperatively for measurement of plasma urea and creatinine, urinary creatinine, retinol binding protein and microalbumin. We found no differences between the mannitol and control patients for any measured variable, and conclude that mannitol has little impact on renal function in patients with normal pre-operative plasma creatinine concentration

Regulation of zebrafish hatching by tetraspanin cd63

Tetraspanins cause the clustering of membrane proteins into a level of organisation essential for cellular function. Given the importance and complicated nature of this mechanism, we attempted a novel approach to identify the function of a single component in a biologically relevant context. A morpholino knockdown strategy was used to investigate the role of cd63, a membrane protein associated with intracellular transport and a melanoma marker, in embryonic zebrafish. By using three separate morpholinos targeting cd63, we were able to identify a specific phenotype. Strikingly, morphant fish failed to hatch due to the lack of secreted proteolytic enzymes required for chorion-softening. The morphology of the hatching gland at both the cellular and intracellular levels was disorganised, suggesting a role for cd63 in the functioning of this organ. This work identifies a specific role for cd63 in the zebrafish embryo and provides evidence for the suitability of zebrafish as a model system for the investigation of tetraspanin enriched microdomains

Non-functioning adrenal incidentalomas are associated with elevated D-dimer levels

Aim: Although the majority of adrenal incidentalomas (Al) are non-functioning, studies evaluating metabolic disturbances in this particular group are limited. The objective of this study is to investigate metabolic syndrome components and levels of plasma von Willebrand factor (VWF), fibrinogen, and D-dimer in subjects with non-functioning Al. Subjects and methods: Forty-five subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders and 37 healthy controls were enrolled. The patients and controls underwent hormonal evaluation including morning cortisol, ACTH, post-dexamethasone suppression test (DST), morning cortisol, DHEAS, and urinary free cortisol. Anthropometric and metabolic parameters and body composition were assessed and fibrinogen, D-dimer, and VWF were measured. Results: When compared with healthy controls, subjects with Al had significant elevations in several metabolic and anthropometric parameters, uric acid, post-DST cortisol, and D-dimer. When compared with body mass index-matched controls, blood pressure (p=0.004), uric acid (p=0.009), post-DST cortisol (p=0.014), and D-dimer (p=0.045) remained significantly elevated. We demonstrated weak correlations between D-dimer and other metabolic and anthropometric variables. Morning cortisol was demonstrated as an independent variable associated with homeostasis model assessment levels in subjects with Al (beta=410, p=0.004). Conclusion: Individuals with clinically and hormonally inactive adrenal adenomas feature insulin resistance and a variety of metabolic disturbances. The subtle cortisol autonomy seems to be associated with insulin-resistant state. D-dimer elevation in Al group was a consequence of insulin-resistant state associated with subtle cortisol autonomy rather than a direct effect of cortisol secretion. (J. Endocrinol. Invest. 32: 338-343, 2009) (C)2009, Editrice Kurti