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  • 11
    Electronic Resource
    Electronic Resource
    Intra- and inter-nephron heterogeneity of gluconeogenesis in the rat: effects of chronic metabolic acidosis and potassium depletion (1986)
    Springer
    Pflügers Archiv 407 (1986), S. 1-7 
    Details
    ISSN: 1432-2013
    Keywords: Renal gluconeogenesis ; Chronic metabolic acidosis ; Potassium depletion ; Microdissected nephron segment ; Superficial nephron ; Juxtamedullary nephron ; Nephron heterogeneity ; Substrate specificity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The intra- and inter-nephron heterogeneity of renal gluconeogenesis within rat proximal tubules and the effects of chronic metabolic acidosis and chronic potassium(K)-depletion were studied using isolated proximal tubules of rats by directly measuring glucose synthesized. The gluconeogenic activity from pyruvate and glutamine in control rats was almost limited to within the early proximal tubule (S1: 45.4±5.7 pmol/mm/60 min from pyruvate; 58.0±6.0 from glutamine). Very low, but detectable gluconeogenesis was observed in the middle portion of the proximal tubule (S2:9.9±2.2 from pyruvate; 4.8±1.1 from glutamine). The rate of glucose production in the terminal proximal tubule (S3) was negligible. Furthermore, gluconeogenesis from glutamine of superficial (SF) nephrons was significantly higher than that of juxtamedullary (JM) ones, whereas no difference was seen in gluconeogenesis from pyruvate. In acidotic and K-depleted rats, significant increase could be seen in S1 and S2, but the increase in S3 was not significant. By the serial determination in acidosis, the glucose production from both substrates was found to be the highest at the second 1 mm segment from the glomerulus, and it decreased downward along the proximal tubule. In acidosis, glucose production from both substrates in SF nephrons and that from glutamine in JM ones were elevated significantly compared with the control, but that from pyruvate in JM nephrons did not change. These results suggest that S1 of the SF nephron plays the most important role in gluconeogenesis in the control, whereas S1 of the JM nephron and S2 contribute to gluconeogenesis in acidotic and/or possibly K-depleted rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00580712
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  • 12
    Electronic Resource
    Electronic Resource
    Stereoselective renal secretion of carbenicillin in rabbits: Role of the organic anion transporter at the renal brush border membrane (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 349-357 
    Details
    ISSN: 0899-0042
    Keywords: carbenicillin ; stereoselective ; secretion ; transport ; rabbit ; membrane vesicles ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Stereoselectivity in the renal secretion of carbenicillin (CBPC) was studied in rabbits. Significant renal secretion of CBPC was observed in vivo, with the secretion of the S-epimer being greater than that of the R-epimer. Stereoselective transport of CBPC was further studied in vitro using basolateral and brush border membrane vesicles prepared from rabbit kidneys. The transport of CBPC by the organic anion transporter into the basolateral membrane vesicles (BLMV) was not stereoselective. In contrast, a distinct stereoselectivity was observed in the transport of CBPC by the organic anion transporter into the brush border membrane vesicles (BBMV), with the transport of the S-epimer being more favorable. Significant epimer-epimer interactions were also observed in the transport into BBMV. The stereoselectivity of the transport of CBPC was calculated from the kinetic parameters with consideration of epimer-epimer interactions and was similar to that observed in vivo. It was concluded that the observed stereoselectivity in the renal secretion of CBPC in vivo reflected that of transport via the organic anion transporter located at the brush border membrane. Chirality 10:349-357, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Stereoselectivity and enantiomer-enantiomer interactions in the binding of ibuprofen to human serum albumin (1997)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 9 (1997), S. 643-649 
    Details
    ISSN: 0899-0042
    Keywords: ibuprofen ; stereoselective ; binding ; HSA ; interaction ; fluorescent ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Binding of ibuprofen (IB) enantiomers to human serum albumin (HSA) was studied using a chiral fluorescent derivatizing reagent, which enabled the measurement of IB enantiomers at a concentration as low as 5 × 10-8 M. Scatchard analyses revealed that there were two classes of binding sites for both enantiomers. For the high affinity site, the number of the binding sites was one for both enantiomers, and the binding constant of R-IB was 2.3-fold greater than that of S-IB. The difference in the affinity at the high affinity site may result in the stereoselective binding of IB enantiomers at therapeutic concentrations. It was confirmed that the high affinity site of IB enantiomers is Site II (diazepam binding site) by using site marker ligands. Also, significant enantiomer-enantiomer interactions were observed in the binding. The binding data were quantitatively analyzed and a binding model with an assumption of competitive interactions only at the high affinity site simulated the binding characteristics of IB enantiomers fairly well. Chirality 9:643-649, 1997. © 1997 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Stereoselective binding of carbenicillin epimers to human serum albumin (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 201-206 
    Details
    ISSN: 0899-0042
    Keywords: carbenicillin ; stereoselective ; binding ; HSA ; interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Binding of carbenicillin (CBPC) epimers to human serum albumin (HSA) was found to be stereoselective. Epimer-epimer interaction was also observed in the binding to HSA. There were at least three binding sites on HSA for CBPC epimers, one of which (stereoselective site) was more in favor of S-CBPC than R-CBPC. At the stereoselective site, the binding constant of S-CBPC was approximately 4-fold greater than that of R-CBPC. The affinities to other binding sites (non-stereoselective sites) were similar between the epimers, and the affinity of S-CBPC of the non-stereoselective sites was much smaller than that for the stereoselective site.R-CBPC and S-CBPC appeared to displace each other at all the binding sites, i.e., the binding of the epimers was competitive at the non-stereoselective sites as well as at the stereoselective site. By using site marker ligands, it was revealed that CBPC epimers may bind to Site I (warfarin binding site), but not to Site II (diazepam binding site). A binding model with an assumption of competitive interactions at all the binding sites simulated the binding characteristics of CBPC epimers fairly well. © 1996 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    A phase II study of (2″ R)-4′ -0-tetrahydropyranyladriamycin (THP) in hematological malignancies (1987)
    Springer
    Investigational new drugs 5 (1987), S. 299-305 
    Details
    ISSN: 1573-0646
    Keywords: THP ; acute leukemia ; malignant lymphoma ; phase II study ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13–34 mg/m2 for 3–5 consecutive days or 35–50 mg/m2 at 3–4 week intervals. Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6. The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for acute leukemia and malignant lymphoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175302
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  • 16
    Electronic Resource
    Electronic Resource
    Transport Characteristics of Ceftibuten, a New Oral Cephem, in Rat Intestinal Brush-Border Membrane Vesicles: Relationship to Oligopeptide and Amino β-Lactam Transport (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 308-312 
    Details
    ISSN: 1573-904X
    Keywords: ceftibuten ; transport ; brush-border membrane ; oligopeptide ; amino β-lactam ; oral cephem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Ceftibuten undergoes H+-coupled uphill transport across rat small intestinal brush-border membrane vesicles. The effects of amino acids, peptides, folate, and β-lactams on the uptake of ceftibuten were examined. Uptake of ceftibuten was competitively inhibited by dipeptides or tripeptides. A counter-transport effect on ceftibuten uptake was observed in the vesicle preloaded with these peptides, and the transport was temporarily against a concentration gradient (overshooting). On the other hand, ceftibuten uptake was not changed by amino acids and a tetrapeptide. Therefore, ceftibuten is predominantly transported via the oligopeptide transport system in the brush-border membranes. The relationship of ceftibuten transport to folate and other oral antibiotics was also investigated. Cyclacillin, cephradine, and cefadroxil exhibited both inhibitory and countertransport effects, but folate, cefaclor, and cephalexin showed only a slight inhibitory effect. As the transport of cefaclor showed no uphill uptake in the presence of a H+ gradient and its H+ stimulated uptake was small, a H+ gradient-independent carrier-mediated system seems to participate in its transport. These findings suggest that two different carrier-mediated transport systems, H+ gradient dependent and independent, may exist for oral cephems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015946407709
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  • 17
    Electronic Resource
    Electronic Resource
    Intrinsic Lymphatic Partition Rate of Mepitiostane, Epitiostanol, and Oleic Acid Absorbed from Rat Intestine (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 1302-1306 
    Details
    ISSN: 1573-904X
    Keywords: mepitiostane ; intrinsic lymphatic partition rate ; intestinal lymphatics ; portal absorption ; epitiostanol ; oleic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Mepitiostane (MP), epitiostanol (EP), and oleic acid were administered to the jejunal loop of mesenteric vein- and thoracic duct-cannulated rats, and the intrinsic lymphatic partition rate (ILPR) of the absorbed compounds was directly determined. When 14C-EP was administered to the jejunal loop, recovery of unchanged EP in the mesenteric blood and the lymph was 7.9 and 0.03% of the administered dose, respectively. In contrast, following administration of 14C-MP, recovery of unchanged MP in the mesenteric blood and the lymph was 1.2 and 15.0%, respectively. Thus, following passage through the mucosal cell, 99.6% of the unchanged EP was partitioned into the blood and 0.4% into the lymph, while for unchanged MP, 7.6% was partitioned into the blood and 92.4% into the lymph. When 14C-oleic acid was administered to the jejunal loop, most of the penetrating oleic acid was incorporated into triglycerides in epithelial cells and transferred exclusively into the lymph. However, of the unchanged oleic acid, only 37.6% was partitioned into the lymph and 62.4% into the blood. The ILPR was 92.4% for MP, 0.4% for EP, and 37.6% for oleic acid. We conclude that the ILPR values indicate the true lymphotropic property of the compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015864131681
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  • 18
    Electronic Resource
    Electronic Resource
    Factors Determining the Intrinsic Lymphatic Partition Rate of Epitiostanol and Mepitiostane (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 1617-1621 
    Details
    ISSN: 1573-904X
    Keywords: mepitiostane ; epitiostanol ; intrinsic lymphatic partition rate ; lipophilicity ; chylomicron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Substitution of the steroid epitiostanol (EP) at position 17 with methoxycyclopentane yields the extremely lipophilic mepitiostane (MP) with preferential partitioning into the lymph. Most of the MP in the lymph was associated with the core lipids of chylomicrons and very low-density lipoproteins (VLDL), as was also the case for EP. However, the dialysis velocity of EP and MP from lymph to plasma differed greatly; EP, but not MP, was transferred from the lymph to the plasma. This difference was attributed to differences in their unbound fraction in the lymph. Lymphatic transfer and the logP value of several tested steroids correlated well. Therefore, the oral EP prodrug, MP, partitioned into the lymph because of its superlipophilicity and resultant retention in the core lipids of chylomicrons and VLDL.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015824710957
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  • 19
    Electronic Resource
    Electronic Resource
    Epimerization Kinetics of Moxalactam in Frozen Urine and Plasma Samples (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 364-369 
    Details
    ISSN: 1573-904X
    Keywords: moxalactam ; epimerization ; frozen plasma ; frozen urine ; electrolyte ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The epimerization of moxalactam (LMOX) in frozen urine and plasma samples was studied during long-term storage. The R/S ratio at equilibrium [(R/S)eq] at −10°C was similar in urine and in rat and human plasma ultrafiltrate but differed from that in water. The (R/S)eq values in human plasma and its ultrafiltrate differed slightly, while they were the same in rat plasma and in its ultrafiltrate. The difference for the human plasma and ultrafiltrate may result from differences in plasma protein binding between R- and S-epimers in the liquid region of the frozen plasma. The change of R/S ratio in frozen human plasma continued below the collapse temperature of LMOX aqueous solution, where the liquid region appeared still to exist as determined by NMR measurement. Consequently, the biological LMOX samples should be preserved at or below −70°C to prevent changes in the R/S ratio.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015815321570
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  • 20
    Electronic Resource
    Electronic Resource
    Elektronenmikroskopische Untersuchungen an Nervenfasern in menschlichen Schweissdrüsen (1960)
    Springer
    Cell & tissue research 52 (1960), S. 129-139 
    Details
    ISSN: 1432-0878
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The nerve supply of the axillary sweat glands was investigated electron microscopically in 8 osmidrosis patients. The following results were obtained: 1. The autonomic peripheral nerve fibers are distributed in the layer of collagen fibers outside the basement membranes of the glandular tubes, and they run parallel to the axis of these tubes. Peripheral autonomic nerve fibers were never seen to pass through the basement membrane and to enter the parenchyma. The axons of the nerve fibers probably make contact with the basement membrane of the sweat glands. 2. No nerve fiber was found in the area of excretory ducts. 3. While running in the Schwann cell cytoplasm, the axons of the nerve fibers fit into excavations of the Schwann cells. A row of Schwann cells, which are elongated and arranged non-syneytially, is covered with numerous collagen fibers. They run parallel to the long axis of the Schwann cells. Occasionally a fibrocyte is seen near the collagen fibers, which are surrounding the Schwann cells. 4. The peripheral nerve fibers bordering the basement membrane of the sweat glands are not ensheathed by fibrocytes. Bundles of nerve fibers are enwrapped cylindrically with endoneurium. 5. When leaving the cytoplasm of one Schwann cell and entering that of the next, the axon never gets out of the layer of collagen fibers surrounding the two Schwann cells. 6. Inside the axoplasm of the peripheral nerve fiber around the sweat glands, there are many synaptic vesicles and mitochondria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00338977
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