Biomedical subjects

F Valencic

Publications and source records attributed to F Valencic.

6 recordsLinked to original sources

PubMed1992

A new porphyrin photosensitizer (PH1008) in model membranes, normal cells, and bladder cancer cells.

Newer photosensitizers continue to be sought for photodynamic therapy of bladder cancer particularly since local rather than systemic application is desired. Recent studies have indicated that a cationic dye, PH1008, a 13,17-N,N,N-dimethylethylethanolamine ester of protoporphyrin, sensitizes the photolysis of red blood cells. The study described in this report was designed to investigate the plasma membrane partitioning of PH1008 model lipid system and to compare partitioning of PH1008 in normal transitional cells and bladder cancer cells in vitro. Partition coefficient (Kp) values characterizing the distribution of PH1008 between aqueous buffer and normal and malignant transitional cells were 3.4 +/- 0.7 x 10(4) (CRL-7881) and 9.5 +/- 1.4 x 10(4) (HTB-9), resulting in a 20% difference in membrane photosensitizer concentration at a particular photosensitizer concentration. Significantly higher (2-5 fold) differences are observed between tumor and surrounding normal tissue for systemically delivered photofrin II. Cell-bound drug was 30-fold (CRL-7881) and 80-fold (HTB-9) more fluorescent when compared to aqueous buffer. The combined effects of partitioning and bound fluorescence suggest that a 3.2-fold increase in fluorescence of transformed vs. normal bladder urothelium exists. This difference in fluorescence suggests that PH1008 might be more useful as a diagnostic tool than as a phototherapeutic agent.

Humans↗

PubMed1991

Cooperativity in the calcium ion-induced quenching of the intrinsic fluorescence of a series of normal and GLA-deficient bovine prothrombin fragment 1 molecules.

Ca2+ titrations of the intrinsic fluorescence of a series of gamma-carboxyglutamic acid (GLA)-deficient bovine prothrombin fragments 1 yield response Hill plot parameters useful for characterization of the metal ion-binding process. 11-, 10-, and 9-GLA fragments 1 exhibit Tm (the (Ca2+)total concentration at which ln (B/F) = 0 in the response Hill plot) values between 0.2 and 0.3 mM. A 22-fold increase in Tm to 5.4 mM is observed for 8-GLA fragment 1. Tm decreases to 3.8 mM for the 7- and 6-GLA proteins. The value of h, about 2.8 +/- 0.2 for 11-, 10-, and 9-GLA fragments 1, abruptly decreases to 1.2-1.3 for 8-, 7-, and 6-GLA fragments 1. The observed degree of quenching induced by saturating levels of calcium ions is affected by both changes in the intrinsic fluorescence of the metal ion-free proteins and in the maximum possible degree of quenching in the presence of calcium. The kinetic characteristics of the calcium ion-induced quenching of the intrinsic fluorescence of 6-GLA fragment 1 are identical to those observed in 10-GLA fragment 1, suggesting that the fluorescence quenching observed in the 6- and 10-GLA fragments 1, while different in magnitude, involves similar processes. Observation of an abrupt change in the relative electrophoretic mobilities of 11- to 9-GLA fragments 1 compared to 8- to 6-GLA fragments 1, in the absence or presence of Ca2+, suggests the existence of a major protein conformation change which occurs concomitantly with the noted changes in Tm and h response Hill plot parameters. Molecular mechanics calculations suggest a structural hypothesis unifying these observations. Central to this model is the presumption of the existence of hydrogen bond-mediated interactions between metal ion-binding sites.

1-Carboxyglutamic Acid↗

PubMed1988

Interleukin-2 self-association.

The self-association of human recombinant interleukin-2 (IL-2) from E. coli was explored. Self-association, with an apparent Kd of 0.6 micromolar, has pronounced effects on (1) the surface exposure of Trp-121, deduced from quenching studies employing potassium iodide and acrylamide, (2) the apparent quantum yield of Trp-121, the fluorescence of Trp-121 in IL-2 aggregates is 4-fold lower than in IL-2 "monomers", and (3) IL-2-mediated phospholipid vesicle fusion/aggregation.

Humans↗

PubMed1986

Verapamil potentiates vagally mediated sinoatrial chronotropic responses in dogs.

A brief burst of electrical stimuli delivered to the vagus nerve during the cardiac cycle elicits a triphasic cardiac chronotropic response. The cardiac cycle length initially increases, then briefly decreases, and subsequently increases again. We studied the effects of a calcium channel blocking agent, verapamil, on these responses to vagal stimulation during sinoatrial nodal rhythm in anesthetized, open-chest dogs. Verapamil increased the basal cardiac cycle length only slightly; however, the primary cardioinhibition was accentuated approximately 40% (from 396 to 555 ms) by verapamil. Neither the acceleratory phase of this triphasic response nor the secondary cardioinhibition was significantly affected by verapamil. These results indicate that verapamil potentiates the initial action of acetylcholine at the sinoatrial node when the vagus is activated with brief stimuli.

Acetylcholine↗

PubMed1984

Effects of ouabain and vagal stimulation on heart rate in the dog.

When the vagus nerves are stimulated with one burst of pulses per minute, but each burst is placed at a different time in the cardiac cycle, a "vagal effect curve" can be derived which displays the changes in cardiac cycle length (CCL) as a function of the elapsed time from the stimulus. This curve consists of a primary and a secondary phase of increased CCL. We performed experiments on open-chest anaesthetised dogs to test the hypothesis that the secondary phase of increased CCL is caused by an increase in the activity of the electrogenic Na+/K+ pump. In animals with a sinoatrial nodal rhythm (SANR), the mean peak values of the primary and secondary phases of increased CCL were 0.48 +/- 0.03 and 0.06 +/- 001 s, respectively, above the prestimulation level (0.52 +/- 0.01 s). Ouabain (40 micrograms X kg-1 iv) did not significantly alter this bimodal response. In animals with an atrioventricular junctional rhythm (AVJR), the peaks of the primary and secondary increases in CCL were 0.55 +/- 0.03 and 1.04 +/- 0.17 s, respectively, above the prestimulation level (0.72 +/- 0.02 s). In animals with AVJR, ouabain markedly attenuated the peak secondary increase in CCL to 19% of the corresponding control value. This attenuation supports the hypothesis that the prominent secondary increase in CCL evoked by a brief vagal stimulus during AVJR is ascribable to an increased activity of the electrogenic Na+/K+ pump.

Animals↗

PubMed1975

Arterial-venous magnesium gradients in hypovolemic shock: an indication of the irreversible state.

Arterial-venous magnesium differences were examined in mongrel dogs stressed with reversible and lethal hypovolemia. Increases in serum Mg with hemorrhage have long been known to occur in both humans and animals, yet, increased blood Mg levels have not been viewed as an indicator of the irreversible shock state. The magnesium gradient was shown to be a good indicator of cell destruction which is consistent with lethal shock.

Animals↗