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D Larsson

Publications and source records attributed to D Larsson.

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Ca2+ uptake through voltage-gated L-type Ca2+ channels by polarized enterocytes from Atlantic cod Gadus morhua.

The presence and localization of voltage-gated Ca2+ channels of L-type were investigated in intestinal cells of the Atlantic cod. Enterocytes were loaded with the fluorescent Ca2+ probe, fure-2/AM and changes in intracellular Ca2+ concentrations ([Ca2+]i) were measured, in cell suspensions, in the presence of high potassium levels (100 mm), BAY K-8644 (5 microM), nifedipine (5 microM) or omega-conotoxin (1 microM). L-type Ca2+ channels were visualized on intestinal sections using the fluorescent dihydropyridine (-)-STBodipy. Depolarization of the plasma membrane produced a rapid (within 5 sec) and transient (at basal levels after 21 sec) increase in [Ca2+]i. BAY K-8644 increased the [Ca2+]i by 7.2%. Cells in a Ca2+-free buffer increased [Ca2+]i after addition of 10 mm Ca2+, and this increase was abolished by nifedipine in both depolarizing and normal medium but not by omega-conotoxin. Single cell experiments using video microscopy revealed that enterocytes remained polarized several hours after preparation and that the Ca2+ entry and extrusion occurred at specific and different regions of the enterocyte outer membrane. Fluorescent staining of L-type Ca2+ channels in the intestinal mucosa showed the most intense staining at the brushborder membrane. These results demonstrate the presence of voltage gated L-type Ca2+ channels in enterocytes from the Atlantic cod. The channels are mainly located at the apical side of the cells, and there is a polarized uptake of Ca2+ into the enterocytes. This suggests that the L-type Ca2+ channels are involved in the transcellular Ca2+ entry into the enterocytes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Physiological concentrations of 24,25-dihydroxyvitamin D3 rapidly decrease the in vitro intestinal calcium uptake in the Atlantic cod, Gadus morhua.

The effects of physiological concentrations of 1,25(OH)2D3 and 24,25(OH)2D3 on the intestinal Ca2+ uptake in the Atlantic cod (Gadus morhua) were investigated. The intestine was perfused, in vitro, both vascularly and through the intestinal lumen, and the Ca2+ influx was measured using 45Ca. At 2.02, 4.04, 10.1, and 20.2 nM 24,25(OH)2D3 decreased the Ca2+ influx across the intestinal mucosa by 21, 31, 34, and 28%, respectively, whereas perfusion with 1,25(OH)2D3 (concentrations: 85.3, 128, 256, and 640 pM) had no effect. The actions of 24,25(OH)2D3 were dose-related, observed within 10 to 25 min, and are concluded to affect intestinal Ca2+ influx via a rapid nongenomic mechanisms; 1,25(OH)2D3 seems to be without transcaltachic effect. Thus, for the rapid, short-term regulation of intestinal calcium uptake in the Atlantic cod, 24,25(OH)2D3 is a more important vitamin D3 metabolite, in contrast to other vertebrates in which 1,25(OH)2D3 is of major importance.

24,25-Dihydroxyvitamin D 3

Phase I study of intraperitoneal carboplatin as adjuvant therapy in early ovarian cancer.

Early stage poor-risk ovarian cancer patients are at considerable risk for recurrent disease. Adjuvant radio- or chemotherapy has been found to improve disease-free and overall survival. Carboplatin, a second generation platinum, is documented comparable in efficacy to cisplatin in patients with advanced ovarian cancer. The toxicity profile is different from that of cisplatin. Dose-limiting toxicity is myelosuppression. The incidence and grade of renal and neurological toxicity is much lower compared with cisplatin, as is nausea and vomiting. Carboplatin given intraperitoneally (ip) is shown to have a favorable theoretical therapeutic advantage compared with iv administration since the peak peritoneal cavity/peak plasma concentration ratio is 18. Patients with early stage ovarian cancer seem suitable for carboplatin ip treatment. The study was designed to find the maximal tolerated dose (MTD). Three new patients were given two courses at each dose level. The MTD found was confirmed with further patients. Carboplatin was given in 2 liters of glucose via a subcutaneous implantable port without removal of fluid from the cavity. The starting dose was 300 mg/m2. Dose-limiting toxicity was thrombocytopenia and leukopenia. Leukocyte and platelet counts were reconstituted within 28 days in all cases. One case of severe but transient nephrotoxicity was observed. MTD was determined to 500 mg/m2.

Carboplatin