Alterations in Intestinal Transport of Oxalate in Disease States

Normally, absorption of oxalate from dietary sources can occur in all segments of the intestinal tract. However, alterations in both the magnitude and direction of oxalate fluxes across the intestine can occur in disease states. In enteric hyperoxaluria, enhanced absorption of oxalate by the large intestine is caused by increased permeability of a shunt conductance induced by malabsorbed bile salts and fatty acids. In this condition, the contribution of a paracellular passive flux of oxalate moving along its electrochemical gradient will predominate when intraluminal concentrations of free oxalate are high. In contrast, in chronic renal failure, secretion of oxalate can occur across both small and large intestine thereby facilitating extrarenal elimination with subsequent degradation by mucosa) substrate-specific microorganisms. Clearly, in recent studies of oxalate transport, the intestine has emerged with an integral role in mass balance of oxalate in health and disease

The Dopamine D3 Receptor Knockout Mouse Mimics Aging-Related Changes in Autonomic Function and Cardiac Fibrosis

Blood pressure increases with age, and dysfunction of the dopamine D3 receptor has been implicated in the pathogenesis of hypertension. To evaluate the role of the D3 receptor in aging-related hypertension, we assessed cardiac structure and function in differently aged (2 mo, 1 yr, 2 yr) wild type (WT) and young (2 mo) D3 receptor knockout mice (D3KO). In WT, systolic and diastolic blood pressures and rate-pressure product (RPP) significantly increased with age, while heart rate significantly decreased. Blood pressure values, heart rate and RPP of young D3KO were significantly elevated over age-matched WT, but similar to those of the 2 yr old WT. Echocardiography revealed that the functional measurements of ejection fraction and fractional shortening decreased significantly with age in WT and that they were significantly smaller in D3KO compared to young WT. Despite this functional change however, cardiac morphology remained similar between the age-matched WT and D3KO. Additional morphometric analyses confirmed an aging-related increase in left ventricle (LV) and myocyte cross-sectional areas in WT, but found no difference between age-matched young WT and D3KO. In contrast, interstitial fibrosis, which increased with age in WT, was significantly elevated in the D3KO over age-matched WT, and similar to 2 yr old WT. Western analyses of myocardial homogenates revealed significantly increased levels of pro- and mature collagen type I in young D3KO. Column zymography revealed that activities of myocardial MMP-2 and MMP-9 increased with age in WTs, but in D3KO, only MMP-9 activity was significantly increased over age-matched WTs. Our data provide evidence that the dopamine D3 receptor has a critical role in the emergence of aging-related cardiac fibrosis, remodeling, and dysfunction

Hematological Parameters of Five Species of Marine Fishes

1. Blood oxygen capacity (BOC). hemoglobin (Hb) content, hematocrit (Hct). red blood cell (RBC) count, and pH were measured in five species of marine fishes which varied in activity from sedentary to fast swimming. 2. BOC and Hb content were correlated with the level of activity for a species. RBC and Hct varied between species and were more weakly correlated with levels of activity. Blood pH did not vary between the species studied. 3. These data suggest that increased BOC is correlated with high levels of activity in fish and that this increase is due to elevated Hb content of the blood. The increased Hb is generally accompanied by an increase in RBC count, so that the average corpuscular hemoglobin (ACH) remains the same

Hematological Parameters of Five Species of Marine Fishes

1. Blood oxygen capacity (BOC). hemoglobin (Hb) content, hematocrit (Hct). red blood cell (RBC) count, and pH were measured in five species of marine fishes which varied in activity from sedentary to fast swimming. 2. BOC and Hb content were correlated with the level of activity for a species. RBC and Hct varied between species and were more weakly correlated with levels of activity. Blood pH did not vary between the species studied. 3. These data suggest that increased BOC is correlated with high levels of activity in fish and that this increase is due to elevated Hb content of the blood. The increased Hb is generally accompanied by an increase in RBC count, so that the average corpuscular hemoglobin (ACH) remains the same

SOLUTE ADJUSTMENTS IN THE COELOMIC FLUID AND MUSCLE FIBERS OF A EURYHALINE POLYCHAETE, NEANTHES SUCCINEA, ADAPTED TO VARIOUS SALINITIES

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Parsing apical oxalate exchange in Caco-2BBe1 monolayers: siRNA knockdown of SLC26A6 reveals the role and properties of PAT-1

The purpose of this investigation was to quantitate the contribution of the anion exchanger PAT-1 (putative anion transporter-1), encoded by SLC26A6, to oxalate transport in a model intestinal epithelium and to discern some characteristics of this exchanger expressed in its native environment. Control (Con) Caco-2 BBe1 monolayers, 6–8 days postseeding, were compared with those transfected with a small interfering RNA targeted to SLC26A6 (A6KD). Radiotracer and Ussing chamber techniques were used to determine the transepithelial unidirectional fluxes of Ox2−, Cl−, and SO42− whereas fluorometric/BCECF measurements of intracellular pH were used to assess HCO3− exchange. PAT-1 was functionally targeted to the apical membrane, and SLC26A6 knockdown reduced PAT-1 protein (>60%) and mRNA (>75%) expression in A6KD. No net flux of Ox2−, Cl−, or SO42− was detected in Con or A6KD monolayers, yet the unidirectional fluxes in A6KD were reduced 50, 35, and 15%, respectively. Cl−-dependent HCO3− efflux from A6KD was reduced 50% compared with Con. The difference between Con and A6KD properties represents that mediated solely by PAT-1, and by this approach we found that PAT-1-mediated oxalate influx and efflux are inhibited equally by mucosal DIDS (EC50 ∼5 μM) and that mucosal Cl− inhibits oxalate uptake with an EC50 < 20 mM. Transepithelial Cl− gradients supported large, DIDS-sensitive net absorptive or secretory fluxes of oxalate in a direction opposite that of the imposed Cl− gradient. The overall symmetry of PAT-1-mediated oxalate exchange suggests that vectorial oxalate transport observed in vivo is principally dependent on the magnitude and direction of counterion gradients