Search PubMed⌕ Search

Biomedical subjects

V Licko

Publications and source records attributed to V Licko.

At least 55 records · Page 3Linked to original sources
PubMed1976

Evaluation of a 'true' fractional removal rate of glucose in man by bolus and simulated-ramp increase of glucose.

An infusion method designed to produce a gradual ramplike rise in plasma glucose levels in man showed that the observed slope of the ramp was not significantly different from the calculated slope only when both of the following parameters were used: 1. When the glucose disappearance rate coefficient (k) was calculated by an incremental method in which the fasting plasma glucose level was subtracted from each plasma glucose value obtained during a standard rapid intravenous glucose tolerance test. This proved to be superior to a contrasting method in which absolute glucose values are used for the semilogarithmic plot of glucose concentration versus time. 2. When the dilution technic was used to estimate directly the volume distribution of glucose rather than relying on standard reference tables that predict glucose distribution space in man. By using these two parameters obtained during standard intravenous glucose tolerance testing, we have shown that it is possible to calculate the rate of glucose infusion required to achieve successfully in man a ramp of plasma glucose of any desired steepness and to characterize the consequent insulin secretion. This simulated ramp increase of glucose provides a potentially useful tool for investigation of the dynamics of islet-cell function in man.

Adult↗
PubMed1975

Ferritin turnover in plasma: an opportunistic use of blood removed during exchange transfusion.

The concentration of plasma ferritin was measured in serial samples of blood removed from six preterm neonates undergoing exchange transfusion for hyperbilirubinemia. The average plasma ferritin concentration in the infants was 218 ng/ml compared with 47 ng/ml in the donors. The mean concentration of ferritin decreased an average of 62 ng/ml during the exchange transfusions. The plasma ferritin half-life was computed to be 2.5 and 5.5 min in the two infants weighing 2,000 and 2,500 g compared with a half-life of 4 min in the rat. In four infants weighing between 1,000 and 1,180 g, the half-life ranged from 9.1 to 34 min. These data support the concept of a rapid plasma ferritin turnover and indicate that ferritin may transport a large amount of iron through the plasma compartment in spite of its low concentration.

Birth Weight↗
PubMedDate not supplied

Efficacy and concentration-response of murine anti-VEGF monoclonal antibody in tumor-bearing mice and extrapolation to humans.

The development of a neovascular supply (angiogenesis) is a major aspect of tumorigenesis. Recent work has indicated that vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis. In vitro and in vivo studies have demonstrated that an anti-VEGF antibody is capable of suppressing the growth of human tumor cell lines. The following study was conducted in tumor-bearing nude mice to evaluate the concentration-response relationship of murine anti-VEGF monoclonal antibody (muMAb VEGF) so that an efficacious plasma concentration of the recombinant humanized form (rhuMAb VEGF) in cancer patients could be estimated. (This study was included in our Investigational New Drug application to support the clinical dosing regimen and projected human safety factors for the toxicology program.) Additionally, the growth dynamics of the tumors were evaluated as a function of dose to explore whether a mechanismic interpretation of tumor growth inhibition by muMAb VEGF is possible. On day 1, A673 human rhabdomyosarcoma cells (2 x 10(6) cells/mouse) were injected subcutaneously in 188 beige nude mice (16-24 g). Treatment with muMAb VEGF (0.05-5.0 mg/kg; n = 24/group), phosphate-buffered saline (n = 10), or anti-gp120 isotype-matched control antibody (5.0 mg/kg; n = 10) began 24 hr later. Each animal received intraperitoneal injections of test material twice weekly for 4 wk. Immediately prior to each dose, 2 mice from each muMAb VEGF group were selected randomly, and plasma was collected for pharmacokinetic evaluation; at the end of the study, samples were collected from all animals for pharmacokinetic evaluation. Tumor dimensions were recorded weekly, and at the end of the study, tumor weight and dimensions were recorded. Satisfactory tumor suppression in nude mice was achieved at muMAb VEGF doses of > or =2.5 mg/kg, where the average trough muMAb VEGF plasma concentration was 30 microg/ml (concentrations in individual animals >10 microg/ml). Assuming the pharmacokinetics of rhuMAb VEGF in patients will resemble the pharmacokinetics of a similar humanized anticancer monoclonal antibodies, a clinical dosing regimen was designed to maintain the rhuMAb VEGF plasma concentration in this efficacious range. This study shows an approach that can be used to estimate a human dosing regimen from preclinical pharmacokinetic/pharmacodynamic data. Because we have just initiated clinical trials with rhuMAb VEGF we cannot judge clinical outcome in relation to these preclinical predictions; nonetheless, it is hoped that by sharing our approach and thought processes with other investigators we can assist the discovery and development of anticancer therapeutics.

Animals↗
PubMedDate not supplied

Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration.

Access of recombinant proteins to the retina following intravitreal administration is poorly understood. A study was conducted in male Rhesus monkeys (15 to 28 mo of age; 2.8-3.3 kg) in order to compare the intraocular tissue distribution, pharmacokinetics, and safety of 125Iodine (I)-labeled full-length humanized rhuMAb HER2 antibody (148 kD) and of 125I-labeled humanized rhuMAb vascular endothelial growth factor Fab antibody (48.3 kD) following bilateral bolus intravitreal injection on day 0 (5 animals/group). The dose administered to each eye was 25 microg (9-10 microCi) in 50 microl. Animals were euthanatized on day 0 (1 hr postdose) and on days 1, 4, 7, and 14. Safety assessment included direct ophthalmoscopy, intraocular pressure measurements, clinical observations, body weight, and hematology and clinical chemistry panels. Blood and vitreous samples were collected daily (blood only) and at necropsy for pharmacokinetics and analysis for antibodies to the test materials; the ocular tissue distribution of the test material was evaluated by microautoradiography. All animals completed the study. Microautoradiography demonstrated that the full-length antibody did not penetrate the inner limiting membrane of the retina at any of the time points examined. In contrast, the Fab antibody fragment diffused through the neural retina to the retinal pigment epithelial layer at the 1-hr time point and persisted in this location for up to 7 days. Systemic exposure to test material was low but variable: the highest plasma concentration of the full-length antibody was 20.3 ng/ml, whereas plasma concentrations for the Fab antibody remained below the limit of quantitation (i.e., <7.8 ng/ml). An immune response to the test material was not evident in either treatment group. The half-life in vitreous was 5.6 days for the full-length antibody and 3.2 days for the Fab antibody. The shorter intravitreal half-life of the Fab antibody is related to its smaller size and its significant diffusion through the retinal layers. The differences in pharmacokinetics and tissue distribution that are noted between the full-length and Fab antibodies in this study identify potential therapeutic approaches that may be exploited in specific disease conditions.

Animals↗