Systemic lupus erythematosus in Aboriginal and Torres Strait Islander peoples in Australia: addressing disparities and barriers to optimising patient care.

The first inhabitants of Australia and the traditional owners of Australian lands are the Aboriginal and Torres Strait Islander peoples. Aboriginal and Torres Strait Islander peoples are two to four times more likely to have systemic lupus erythematosus (SLE) than the general Australian population. Phenotypically, SLE appears distinctive in Aboriginal and Torres Strait Islander peoples and its severity is substantially increased, with mortality rates up to six times higher than in the general Australian population with SLE.

Real-world experience of metformin use in pregnancy: Observational data from the Northern Territory Diabetes in Pregnancy Clinical Register.

Background: In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register.

Interactions between zinc deficiency and environmental enteropathy in developing countries.

Zinc deficiency affects one-fifth of the world's population and leads to substantial morbidity and mortality. Environmental enteropathy (EE), a subclinical pathology of altered intestinal morphology and function, is almost universal among people living in developing countries and affects long-term growth and health. This review explores the overlapping nature of these 2 conditions and presents evidence for their interaction.

[Pumpless extracorporeal lung assist].

The recently introduced pumpless extracorporeal lung assist (PECLA) is a remarkable alternative to the conventional extracorporeal membrane oxygenation in case of severe lung failure. By establishing a shunt between femoral artery and vein using the arterio-venous pressure gradient as a driving force through a low-resistance membrane oxygenator, PECLA provides highly effective gas-exchange by preserved cardiac function. Due to its closed system, reduced priming volume and low heparin demand, the unfavourable effects of extracorporeal membrane oxygenation can be effectively diminished.

[The principles of minimal extracorporeal circulation and its uses].

The recently introduced minimal extracorporeal circulation system is a remarkable alternative to the conventional heart-lung machine in several cardiosurgical indications. It consists of a centrifugal pump, an oxygenator, a tip-to-tip heparin coated line set and a modified cell saver application. Due to its closed blood-air interaction-free construction and reduced priming volume, the unfavourable effects of perfusion as haemodilution, inflammatory response, locoregional malperfusion, transfusion needs, can be effectively reduced.

Efflux of dietary flavonoid quercetin 4'-beta-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance-associated protein-2.

Although there is strong evidence to suggest that flavonoid consumption is beneficial to human health, the extent to which flavonoids are absorbed and the mechanisms involved are controversial. Contrary to common dogma, we previously demonstrated that quercetin 4'-beta-glucoside, the predominant form of the most abundant dietary flavonoid, quercetin, was not absorbed across Caco-2 cell monolayers. The aim of this study was to test the hypothesis that a specific efflux transporter is responsible for this lack of absorption.

Functional comparison of the NAD binding cleft of ADP-ribosylating toxins.

Although a common core structure forms the active site of ADP-ribosylating (ADPRT) toxins, the limited-sequence homology within this region suggests that different mechanisms are being used by toxins to perform their shared function. To explain differences in their mechanisms of NAD binding and hydrolysis, the functional interrelationship of residues predicted to perform similar functions in the beta3-strand of the NAD binding cleft of different ADPRT toxins was compared. Replacing Tyr54 in the A-subunit of diphtheria toxin (DTA) with a serine, its functional homologue in cholera toxin (CT), resulted in the loss of catalytic function but not NAD binding.

Effects of diabetes and hyperglycemia on the hexosamine synthesis pathway in rat muscle and liver.

In vitro studies suggested that increased flux of glucose through the hexosamine biosynthesis pathway (HexNSP) contributes to glucose-induced insulin resistance. Glutamine:fructose-6- phosphate amidotransferase (GFAT) catalyzes glucose flux via HexSNP; its major products are uridine diphosphate (UDP)-N-acetyl hexosamines (UDP-HexNAc). We examined whether streptozotocin (STZ)-induced diabetes (4-10 days) or sustained hyperglycemia (1-2 h) in normal rats alters absolute or relative concentrations of nucleotide-linked sugars in skeletal muscle and liver in vivo.

Na(+)-Ca2+ exchanger in arteries: identification by immunoblotting and immunofluorescence microscopy.

Antibodies raised against dog cardiac Na(+)-Ca2+ exchanger were employed to determine the presence and distribution of the exchanger in arterial smooth muscle (ASM) cells. The antiserum cross-reacted with protein bands of approximately 70, 120, and 150-160 kDa from the membranes of ASM cells, as well as heart sarcolemma. A cardiac Na(+)-Ca2+ exchanger cDNA probe hybridized to 7-kilobase (kb) mRNA from myocytes of the mesenteric artery.

Production and characterization of soluble and transmembrane murine CD2. Demonstration that CD48 is a ligand for CD2 and that CD48 adhesion is regulated by CD2.

The baculovirus expression vector was used to produce full length, two amino-terminal Ig-like extracellular domains, and one amino-terminal Ig-like extracellular domain soluble murine CD2 products. The products were monomeric, glycosylated, and of the correct predicted m.w.

Presynaptic localization of sodium/calcium exchangers in neuromuscular preparations.

Calcium ions play a critical role in neurotransmitter release. The cytosolic Ca2+ concentration ([Ca2+]cyt) at nerve terminals must therefore be carefully controlled. Several different mechanisms, including a plasmalemmal Na/Ca exchanger, are involved in regulating [Ca2+]cyt.

Immunofluorescence localization of the Na-Ca exchanger in heart cells.

We investigated the localization of the Na-Ca exchanger in fixed, isolated heart cells from rat and guinea pig using immunocytochemical methods with epifluorescence and confocal microscopy. We found that the Na-Ca exchanger is distributed throughout all membranes in contact with the extracellular space, including the sarcolemma, the transverse tubules (T-tubules), and the intercalated disks. Microscopic nonuniformities in the fluorescent labeling appear to reflect varying views of the membranes containing Na-Ca exchanger protein.

Sequential use of detergents for solubilization and reconstitution of a membrane ion transporter.

Solubilization and reconstitution of the cardiac sarcolemmal Na+/Ca2+ exchanger by use of the anionic detergent cholate and its application for reconstitution of the exchanger following solubilization with zwitterionic or nonionic detergents is described. Solubilization and reconstitution with cholate provided a 32.6-fold enrichment of Na+/Ca2+ exchange activity over sarcolemmal vesicles (5.

Gender differences of human tissue kallikrein and an erythrocyte kallikrein-like enzyme in essential hypertension.

The level of tissue kallikrein in serum and urine, and of an erythrocyte kallikrein-like enzyme, were compared in 10 subjects without hypertension and in 10 patients with hypertension with normal renin levels. Each group consisted of five men and five women. All subjects were observed at a general clinical research center for consecutive 5- to 6-day periods of daily dietary sodium intake of 109, 9, and 259 mEq.

Relationship between steady-state depression of calcium-dependent action potentials and competition for binding sites by nifedipine, nitrendipine, and PY 108-068.

The objective of the present study was to determine the time-courses for depression and recovery of calcium-mediated action potentials in canine Purkinje fibers following exposure to dihydropyridine (DHP) calcium channel antagonists and to determine if the reported discrepancy (up to 1,000 X) between I50 values for inducing physiologic effects in isolated tissues and the dissociation constant (Kd) for [3H]nitrendipine binding to membrane sites could be reduced when physiologic measurements were made under experimentally determined steady-state conditions. Changes in dV/dtmax of slow calcium-mediated action potentials (20 mM KCl, 10(-6) M isoproterenol) were recorded at 10-min intervals during exposure (2-4 h) to nifedipine, nitrendipine, and PY 108-068 (10(-9) M-4 X 10(-8) M). Time to steady state was slow, with half-life t1/2 values of 40 min (nifedipine), 84 min (nitrendipine), and 81 min (PY 108-068).

Effects of membrane potential on sodium-dependent calcium uptake by sarcolemma-enriched preparations from canine ventricle.

The effect of membrane potential on sodium-dependent calcium uptake by vesicles in an isolated cardiac sarcolemma preparation was examined. Initial time course studies showed that the reaction deviated from initial velocity conditions within minutes. This appeared to be due, in part, to loss of the sodium gradient.

Sodium-sensitive calcium binding to sarcolemma-enriched preparations from canine ventricle.

Calcium binding to sarcolemma-enriched preparations from canine ventricle was evaluated. The preparation was exposed to calcium and 45Ca at physiological ionic strength, pH 7.4, for 15-18 hours at 5 degrees C.

Sodium and potassium permeability of membrane vesicles in a sarcolemma-enriched preparation from canine ventricle.

Vesicles in a highly enriched sarcolemma preparation from canine ventricle were found to develop membrane potentials in response to outwardly directed potassium and inwardly directed sodium concentration gradients. The magnitude of the potential measured by the fluorescent dye diS-C3-(5) suggested a sodium-to-potassium permeability ratio between 0.2 and 1.

Voltage-sensitive calcium flux promoted by vesicles in an isolated cardiac sarcolemma preparation.

The effect of membrane potential on the vesicular uptake of calcium in an isolated cardiac sarcolemma preparation from canine ventricle was evaluated. Membrane potentials were developed by the establishment of potassium gradients across the vesicular membranes. In the presence of valinomycin, the fluorescence changes of the voltage sensitive dye, diS-C3-(5) were consistent with the development of potassium equilibrium potentials.