Ronald Tudball

Bio: Ronald Tudball is an academic researcher from Monash Medical Centre. The author has contributed to research in topics: Bolus (medicine) & Vitamin D and neurology. The author has an hindex of 3, co-authored 6 publications receiving 138 citations. Previous affiliations of Ronald Tudball include Monash University.

Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans.

Abstract: Continuous release of nitric oxide contributes to the maintenance of resting tone in the human forearm and coronary circulations; however, evidence for a similar role of vasodilator prostanoids suc...

Vitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants

Abstract: Aim There are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation. Methods This single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium. Results Of 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131–177) was higher than the daily group (48 nmol/L, 95% CI 42–54) at 1–2 weeks of age. This was reversed at 3–4 months, (65 nmol/L, 95% CI 59–71) compared with the daily group (81 nmol/L, 95% CI 77–85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1–2 weeks. By 3–4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1–2 weeks (2.73 mmol/L) and 3–4 months (2.55 mmol/L). Conclusion Single bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1–2 weeks of age compared with daily dosing, but repletion rates were similar by 3–4 months. There was no hypercalcaemia documented with single bolus dosing in this study.

What's Wrong with the Transferrin?

Abstract: A 2-year-old boy presented with developmental delay and rapidly progressing spasticity of lower limbs. A serum transferrin isoform test was requested as a work-up for congenital disorders of glycosylation (CDG). Figure 1 shows his serum transferrin isoelectric focusing pattern. Fig. 1. Lanes A–C, isoelectric focusing without neuraminidase; lanes D–F, isoelectric focusing after in vitro treatment of serum with neuraminidase. Lane A, normal serum; lane B, CDG type 1 patient; lane C, this patient; lane D, this patient; lane …

EDHF: an update

Abstract: The endothelium controls vascular tone not only by releasing NO and prostacyclin, but also by other pathways causing hyperpolarization of the underlying smooth muscle cells. This characteristic was at the origin of the term 'endothelium-derived hyperpolarizing factor' (EDHF). However, this acronym includes different mechanisms. Arachidonic acid metabolites derived from the cyclo-oxygenases, lipoxygenases and cytochrome P450 pathways, H(2)O(2), CO, H(2)S and various peptides can be released by endothelial cells. These factors activate different families of K(+) channels and hyperpolarization of the vascular smooth muscle cells contribute to the mechanisms leading to their relaxation. Additionally, another pathway associated with the hyperpolarization of both endothelial and vascular smooth muscle cells contributes also to endothelium-dependent relaxations (EDHF-mediated responses). These responses involve an increase in the intracellular Ca(2+) concentration of the endothelial cells, followed by the opening of SK(Ca) and IK(Ca) channels (small and intermediate conductance Ca(2+)-activated K(+) channels respectively). These channels have a distinct subcellular distribution: SK(Ca) are widely distributed over the plasma membrane, whereas IK(Ca) are preferentially expressed in the endothelial projections toward the smooth muscle cells. Following SK(Ca) activation, smooth muscle hyperpolarization is preferentially evoked by electrical coupling through myoendothelial gap junctions, whereas, following IK(Ca) activation, K(+) efflux can activate smooth muscle Kir2.1 and/or Na(+)/K(+)-ATPase. EDHF-mediated responses are altered by aging and various pathologies. Therapeutic interventions can restore these responses, suggesting that the improvement in the EDHF pathway contributes to their beneficial effect. A better characterization of EDHF-mediated responses should allow the determination of whether or not new drugable targets can be identified for the treatment of cardiovascular diseases.

Endothelium-mediated control of vascular tone: COX-1 and COX-2 products

Abstract: Endothelium-dependent contractions contribute to endothelial dysfunction in various animal models of aging, diabetes and cardiovascular diseases. In the spontaneously hypertensive rat, the archetypal model for endothelium-dependent contractions, the production of the endothelium-derived contractile factors (EDCF) involves an increase in endothelial intracellular calcium concentration, the production of reactive oxygen species, the predominant activation of cyclooxygenase-1 (COX-1) and to a lesser extent that of COX-2, the diffusion of EDCF towards the smooth muscle cells and the subsequent stimulation of their thromboxane A2-endoperoxide TP receptors. Endothelium-dependent contractions are also observed in various models of hypertension, aging and diabetes. They generally also involve the generation of COX-1- and/or COX-2-derived products and the activation of smooth muscle TP receptors. Depending on the model, thromboxane A2, PGH2, PGF2α, PGE2 and paradoxically PGI2 can all act as EDCFs. In human, the production of COX-derived EDCF is a characteristic of the aging and diseased blood vessels, with essential hypertension causing an earlier onset and an acceleration of this endothelial dysfunction. As it has been observed in animal models, COX-1, COX-2 or both isoforms can contribute to these endothelial dysfunctions. Since in most cases, the activation of TP receptors is the common downstream effector, selective antagonists of this receptor should curtail endothelial dysfunction and be of therapeutic interest in the treatment of cardiovascular disorders. LINKED ARTICLES This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-3

Global prevalence and disease burden of vitamin D deficiency: a roadmap for action in low- and middle-income countries.

Abstract: Vitamin D is an essential nutrient for bone health and may influence the risks of respiratory illness, adverse pregnancy outcomes, and chronic diseases of adulthood. Because many countries have a relatively low supply of foods rich in vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from sunlight, an important proportion of the global population is at risk of vitamin D deficiency. There is general agreement that the minimum serum/plasma 25-hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D deficiency-related bone disease is approximately 30 nmol/L; therefore, this threshold is suitable to define vitamin D deficiency in population surveys. However, efforts to assess the vitamin D status of populations in low- and middle-income countries have been hampered by limited availability of population-representative 25(OH)D data, particularly among population subgroups most vulnerable to the skeletal and potential extraskeletal consequences of low vitamin D status, namely exclusively breastfed infants, children, adolescents, pregnant and lactating women, and the elderly. In the absence of 25(OH)D data, identification of communities that would benefit from public health interventions to improve vitamin D status may require proxy indicators of the population risk of vitamin D deficiency, such as the prevalence of rickets or metrics of usual UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20% prevalence of 25(OH)D 1%), food fortification and/or targeted vitamin D supplementation policies can be implemented to reduce the burden of vitamin D deficiency-related conditions in vulnerable populations.

Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. author's reply

Abstract: BACKGROUND The vascular endothelium contributes to smooth muscle relaxation by tonic release of nitric oxide. To investigate the contribution of nitric oxide to human coronary epicardial and microvascular dilation during conditions of increasing myocardial oxygen requirements, we studied the effect of inhibiting nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) on the coronary vasodilation during cardiac pacing in patients with angiographically normal coronary arteries with and without multiple risk factors for coronary atherosclerosis. METHODS AND RESULTS In 26 patients with angiographically normal or near-normal epicardial coronary arteries, metabolic vasodilation was assessed as a change in coronary vascular resistance and diameter during cardiac pacing (mean heart rate, 141 beats per minute). Endothelium-dependent vasodilation was estimated with intracoronary acetylcholine and endothelium-independent dilation with intracoronary sodium nitroprusside and adenosine. These measurements were repeated after 64 mumol/min intracoronary L-NMMA. At rest, L-NMMA produced a 16 +/- 25% (mean +/- SD) increase in coronary vascular resistance (P < .05) and an 11% reduction in distal epicardial coronary artery diameter (P < .01), indicating tonic basal release of nitric oxide from human coronary epicardial vessels and microvessels. Significant inhibition of pacing-induced metabolic coronary vascular dilation occurred with L-NMMA, coronary vascular resistance was 38 +/- 56% higher (P < .03), and epicardial coronary dilation during control pacing (9 +/- 13%) was converted to constriction after L-NMMA and pacing (-6 +/- 9%, P < .04). L-NMMA specifically inhibited endothelium-dependent vasodilation with acetylcholine (coronary vascular resistance was 72% higher [P < .01]) but did not alter endothelium-independent dilation with sodium nitroprusside and adenosine. Nine patients had no major risk factors for atherosclerosis, defined as serum cholesterol > 240 mg/dL, hypertension, or diabetes. The remaining 17 patients with one or more of these risk factors had depressed microvascular vasodilation during cardiac pacing (coronary vascular resistance decreased by 13% versus 36% in those without risk factors, P < .05). The inhibitory effect of L-NMMA on pacing-induced coronary epicardial and microvascular vasodilation was observed only in patients without risk factors, whereas those with risk factors had an insignificant change, indicating that nitric oxide contributes significantly to pacing-induced coronary vasodilation in patients free of risk factors and without endothelial dysfunction. Patients with risk factors also had reduced vasodilation with acetylcholine (40 +/- 28% versus 68 +/- 8% decrease in coronary vascular resistance, P < .01), but the responses to sodium nitroprusside were similar in both groups. CONCLUSIONS During metabolic stimulation of the human heart, nitric oxide release contributes significantly to microvascular vasodilation and is almost entirely responsible for the epicardial vasodilation. This contribution of nitric oxide is reduced in patients exposed to risk factors for coronary atherosclerosis and leads to a net reduction in vasodilation during stress. An important implication of these findings is that reduced nitric oxide bioavailability during stress in patients with atherosclerosis or risk factors for atherosclerosis may contribute to myocardial ischemia by limiting epicardial and microvascular coronary vasodilation.