Ion transport by the cortical and outer medullary collecting tubule

Anatomy and cell morphology. The rabbit collecting tubule originates near the surface of the kidney, descends through the cortex within the medullary rays and traverses the outer medulla as an unbranched structure. The cortical collecting tubule (CCT) receives the contents of an average of 6 nephrons [1]. The fusion of these nephrons generally occurs proximal to the origins of the collecting tubule. Thus, the collecting tubule is unbranched from the superficial portion of the cortex until it reaches the inner medulla where the collecting tubules begin to fuse to form larger and larger ducts eventually exiting through the papillary tip. Figure 1 schematically represents the collecting tubule as it courses through the cortex and medulla. The fact that the cortical and outer medullary collecting tubule (OMCT) in the rabbit are unbranched facilitates their examination using the technique of in vitro perfusion of isolated nephron segments

Mineralocorticoid effect on K+ permeability of the rabbit cortical collecting tubule

Mineralocorticoid effect on K+ permeability of the rabbit cortical collecting tubule. Mineralocorticoid hormones stimulate Na+ absorption and K+ secretion by the cortical collecting tubule. There is good evidence that this stimulation involves increasing luminal membrane Na+ permeability and the turnover rate (or number) of the Na+-K+ pumps. These experiments were designed to examine whether mineralocorticoid hormones also increase cell K+ permeability. Using 42K tracer measurements in tubules treated with amiloride to inhibit active Na+ and K+ transport, passive K+ permeation increased with increasing mineralocorticoid effect. Net Na+ absorption and the (passive) K+efflux rate coefficient (KK) showed a linear relationship. The stimulatory effect was evident in vitro since 0.2 µM aldosterone added to the bath of tubules harvested from NaCl-loaded rabbits increased KK at 3hrs while time controls showed no change. Since these tubules were also treated with amiloride, this increase in KK was not dependent on increasing Na+ absorption. The results indicate that in addition to the well-described effects of aldosterone on Na+ permeability and cell metabolism, the mineralcorticoid effect includes an increase in cellular K+ permeability

A Na-K-Cl cotransporter in isolated rat papillary collecting duct cells

A Na-K-Cl cotransporter in isolated rat papillary collecting duct cells. Lactate production and ion fluxes were measured in isolated rat papillary collecting duct cells (PCD) to gain further insight into the transport properties of the papillary collecting duct. Lactate production was found to be inhibited by bumetanide in a dose-dependent manner, a maximum inhibition of 22% was obtained at 10−4 M bumetanide and an apparent Ki of 10−8 M was determined. Bumetanide inhibition of lactate production was dependent on the presence of sodium and chloride. Chloride removal inhibited lactate production also by 20%. Bumetanide (10−4 M) inhibited by 35% sodium uptake into PCD cells exposed to 10mM ouabain and chloride uptake into ion depleted PCD cells by 40%. In addition, this bumetanide-sensitive chloride uptake was dependent on the presence of sodium and potassium in the incubation medium. Furthermore, 86Rb uptake into these cells was significantly reduced in the presence of 10−4 M bumetanide. These data provide evidence for the operation of a Na-K-Cl cotransport system in rat papillary collecting duct cells. This transport system might be involved in active chloride transport in the papillary collecting duct and/or volume regulation of the PCD cells

False-negative Histoplasma antigen in acute pulmonary histoplasmosis: the value of urinary concentration by ultrafiltration and heat denaturation of serum proteins in detection of Histoplasma antigen

We report an infant with localized pulmonary histoplasmosis in whom Histoplasma antibody assays, quantitative Histoplasma urine and serum antigen concentrations, and histopathologic findings of a mediastinal mass were nondiagnostic. A provisional diagnosis of histoplasmosis was established by using laboratory methods that increase the sensitivity of the antigen assay using ultrafiltration of urine and ethylenediaminetetraacetic acid/heat denaturation of serum proteins

Factors influencing participation in randomised clinical trials among patients with early Barrett's neoplasia: a multicentre interview study

OBJECTIVES: Strong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett's neoplasia. This paper aims to identify factors influencing patients' participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy. DESIGN: A semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes. SETTING: Interview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted. PARTICIPANTS: We interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined. RESULTS: Four themes were identified centred around interviewees' decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant-recruiter relationship; (2) participants' views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants' perceptions of surgical risks versus less invasive treatments. CONCLUSION: We identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett's-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials

The Cytotoxicity and Mode of Action of 2,3,4-Trisubstituted Pyrroles and Related Derivatives in Human Tmolt4 Leukemia Cells

4-Carbechoxy-l-methyl-2-phenacyl-3-phenylpyrrole (9), 4-carbethoxy-2-(4-methoxybcnzoyl)-3-(4-methoxyphcnyl)pyrrole (10) and 2-(4-methoxybenzoyl)-3,4-bis-(4-methoxyphenyl)pyrrole (11) proved to be potent cytotoxic agents against the growth of murine and human leukemias and lymphomas. Selective toxicity was demonstrated against the growth of solid tumors, e.g. human adenocarcinoma of the colon SW480 and ileum HCT-8, glioma U-87-MG, and rat UMR-106 osteosarcoma. A mode of action study in Tmolt4 leukemia cells demonstrated that the agents inhibited de novo purine synthesis at the regulatory sites PRPP-amido transferase, IMP dehydrogenase as well as dihydrofolate reductase resulting in significant inhibition of DNA synthesis in 60 min. Other biochemical sites which were affected significantly were thymidylate synthetase, DNA polymerase a, RNA polymerases, nucleoside kinase and ribonucleoside reductase