Potential role of purinergic signaling in lithium-induced nephrogenic diabetes insipidus.

Lithium (Li)-induced nephrogenic diabetes insipidus (NDI) has been attributed to the increased production of renal prostaglandin (PG)E(2). Previously we reported that extracellular nucleotides (ATP/UTP), acting through P(2y2) receptor in rat medullary collecting duct (mCD), produce and release PGE(2). Hence we hypothesized that increased production of PGE(2) in Li-induced NDI may be mediated by enhanced purinergic signaling in the mCD.

Potential role of purinergic signaling in urinary concentration in inner medulla: insights from P2Y2 receptor gene knockout mice.

Osmotic reabsorption of water through aquaporin-2 (AQP2) in the inner medulla is largely dependent on the urea concentration gradients generated by urea transporter (UT) isoforms. Vasopressin (AVP) increases expression of both AQP2 and UT-A isoforms. Activation of the P2Y2 receptor (P2Y2-R) in the medullary collecting duct inhibits AVP-induced water flow.

Acute peritonitis in a C57BL/6 mouse model of peritoneal dialysis.

Studies using animal models of peritoneal dialysis (PD) have commonly induced acute peritonitis by intraperitoneal (IP) administration of lipopolysaccharide (LPS). We compared the effects of peritonitis induced by IP administration of either LPS or zymosan on inflammatory parameters [dialysate leukocyte counts and dialysate concentrations of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF)] and peritoneal transport of fluid, small solutes (glucose), and macromolecules (total protein) in a mouse model of PD. Eighteen hours after induction of peritonitis, mice were studied by injecting 2 mL of 4.

Enhanced local production of vascular endothelial growth factor is not sufficient to increase peritoneal permeability to protein during acute peritonitis.

Dialysate concentrations of inflammatory mediators and growth factors, such as vascular endothelial growth factor (VEGF), are increased during acute peritonitis in peritoneal dialysis patients; however, it can be difficult to determine whether these high concentrations are caused by either increased peritoneal permeability or enhanced local production within peritoneal tissues. VEGF and total protein kinetics were first compared in a rabbit model during an 8-h dwell of dialysis solution containing 2.5% dextrose with (peritonitis) and without (control) the addition of 1-2 x 10(5) colony forming units (cfus) of Escherichia coli (series 1 experiments).

Dialyzer clearances and mass transfer-area coefficients for small solutes at low dialysate flow rates.

New daily hemodialysis therapies operate at low dialysate flow rates to minimize dialysate volume requirements; however, the dependence of dialyzer clearances and mass transfer-area coefficients for small solutes on dialysate flow rate under these conditions have not been studied extensively. We evaluated in vitro dialyzer clearances for urea and creatinine at dialysate flow rates of 40, 80, 120, 160, and 200 ml/min and ultrafiltration flow rates of 0, 1, and 2 l/h, using a dialyzer containing PUREMA membranes (NxStage Medical, Lawrence, MA). Clearances were measured directly across the dialyzer by perfusing bovine blood with added urea and creatinine single pass through the dialyzer at a nominal blood flow rate of 400 ml/min.

Effects of anaesthesia on fluid and solute transport in a C57BL6 mouse model of peritoneal dialysis.

Background: Genetically modified mice show promise as animal models for studying the physiology and pathophysiology of the peritoneum during peritoneal dialysis (PD). Methods for evaluation of the functional characteristics of the mouse peritoneum have not been studied extensively, and the effects of anaesthesia on fluid and solute transport in mouse models of PD are unknown.

Methods: A single exchange of dialysis solution was performed in C57BL6 mice by injecting fluid into the peritoneal cavity using a 27-gauge needle and allowing fluid to dwell for 30, 60 or 120 min.

Arterial and venous smooth-muscle cells differ in their responses to antiproliferative drugs.

Arteriovenous polytetrafluoroethylene (PTFE) grafts used for hemodialysis often fail as the result of myointimal hyperplasia with vascular smooth-muscle-cell (SMC) proliferation. The stenotic lesions occur primarily at the graft-vein anastomosis and less frequently at the graft-artery anastomosis. To explore the potentials of pharmacologic agents in preventing hemodialysis-graft stenosis, we first examined the susceptibility of venous and aortic SMCs to 3 antiproliferative drugs.

In vitro pharmacological inhibition of human vascular smooth muscle cell proliferation for the prevention of hemodialysis vascular access stenosis.

Background: Vascular access for chronic hemodialysis often fails as a result of stenosis caused primarily by the proliferation of vascular smooth muscle cells (VSMC). Various drugs have been shown to inhibit the proliferation of VSMC under different conditions.

Methods: In this study, we compared the inhibitory effect of ten drugs on the proliferation of human aortic smooth muscle cells (SMC) in culture.

Hollow fiber shape alters solute clearances in high flux hemodialyzers.

The mass transfer properties of hemodialyzers containing hollow fiber membranes are known to be influenced by membrane chemical composition, surface area, and pore size; however, the effects of hollow fiber shape (or configuration) and packing density within the dialyzer housing have not been well characterized. We determined, both in vitro and ex vivo (clinical), solute clearances and mass transfer-area coefficients (KoA) for high flux dialyzers containing polysulfone hollow fibers of identical chemical composition but different shapes. Hemoflow F80A (1.

Effect of indomethacin on peritoneal protein loss in a rabbit model of peritonitis.

Background: Although various inflammatory mediators have been previously shown to be released into the peritoneal cavity during peritonitis in peritoneal dialysis patients, those that are involved in governing changes in peritoneal permeability to small solutes and protein remain incompletely defined.

Methods: We determined the importance of prostanoid production in the enhanced protein loss observed during acute peritonitis by inhibition experiments using indomethacin, an inhibitor of cyclooxygenase activity. The association between changes in peritoneal permeability and the generation of inflammatory mediators after adding Escherichia coli to peritoneal dialysate was first examined in series 1 experiments.

Increased protein loss during peritonitis associated with peritoneal dialysis is neutrophil dependent.

Background: Peritonitis in peritoneal dialysis patients is accompanied by an enhanced migration of neutrophils (PMNs) and increased protein loss into the peritoneal cavity; however, the role of PMNs in governing increased protein loss during peritonitis associated with peritoneal dialysis is unknown.

Methods: We determined the importance of PMNs in governing changes in peritoneal permeability to protein in New Zealand White rabbits in which acute peritonitis was induced by adding 4 x 106 colony-forming units of Escherichia coli to 35 mL/kg of 0.9% saline dialysate.

The effects of heparin, protamine, and heparinase 1 on platelets in vitro using whole blood flow cytometry.

Unlabelled: The effects of heparinization and the reversal of heparin activity on platelet function after cardiopulmonary bypass have not been well defined. Flow cytometry has become a convenient and powerful technique for characterizing platelets. We examined the expression of a secretion marker (P-selectin) and an aggregation marker (activated fibrinogen receptor GP IIb-IIIa) on normal platelets in response to heparin, heparinase 1, and protamine in vitro using whole blood flow cytometry.

The effects of aprotonin on platelets in vitro using whole blood flow cytometry.

Unlabelled: We sought to evaluate the effects of aprotinin on the number and function of the platelet glycoprotein (GP) IIb-IIIa receptor and on the expression of P-selectin in vitro in order to gain insight into the potential mechanisms involved in the platelet-protective action of aprotinin during cardiopulmonary bypass. Aprotinin at 50 to 200 kallikrein inhibiting units/mL decreased the expression of activated GP IIb-IIIa complex in response to adenosine diphosphate or thrombin receptor activator peptide 6 in a dose-dependent manner in both citrated and heparinized whole blood experiments. Aprotinin inhibited adenosine diphosphate-induced platelet aggregation, but it exhibited no effect on the expression of GP IIIa and P-selectin.

Immunomodulation in vivo by the Mycoplasma arthritidis superantigen, MAM.

Mycoplasma arthritidis produces a potent superantigen (MAM) that activates specific murine and human T lymphocytes to proliferate and secrete lymphokines. We show here that MAM also influences both T- and B-cell functions in vivo. Lymphocytes from mice injected with MAM exhibit a suppression of proliferative responses to MAM in vitro but only a partial suppression of responses to other mitogens.

Discordance of T-cell receptor beta-chain genes in familial multiple sclerosis.

Restriction fragment length polymorphisms of the T-cell receptor beta-chain gene were studied in DNA obtained from 96 individuals from 14 multiplex families with multiple sclerosis (MS). Thirty-four family members had definite MS and two had probable MS. Five normal family members had abnormal findings on cranial magnetic resonance imaging (MRI) scans.

Epidermal growth factor increases granulation tissue formation dose dependently.

Recent studies have shown that epidermal growth factor (EGF) stimulated the rate of formation of granulation tissue in a model of wound repair (A. Buckley, et al., Proc.

Sustained release of epidermal growth factor accelerates wound repair.

Epidermal growth factor (EGF) is a potent mitogen in vitro, but its biological role is less clear. The vulnerary effects of EGF were evaluated in a model of wound repair, the polyvinyl alcohol sponge implanted subcutaneously in rats. EGF was purified to homogeneity by reverse-phase HPLC and quantified by receptor binding assay and amino acid analysis.