Search

Cirrhosis, hepatocellular carcinoma, and other serious liver diseases are caused by the hepatitis C virus (HCV) infection. An oral NS5B inhibitor for the therapy of HCV called Sofosbuvir has received approval. However, its high cost and numerous side effects are emphasized. Therefore, alternative HCV cures that are affordable and side-effect-free must be explored. This research aimed at screening novel bioactive plant molecules as potent HCV inhibitors from databases by exploring the drug kinetic model through the molecular docking, ADMET prediction, density functional theory (DFT) and dynamics simulation approach to identify lead compounds and gave insight into the mechanism of its reaction. The findings indicated that 4 out of 80 screened compounds were chosen as active candidate hits with the most active molecule having PubChem CID 5280445 which is Flavonoid isolated from Eclipta alba displaying the best pharmacokinetics characteristics and kinetic potency as compared with the standard drug sofosbuvir. The compounds' recommendation for a confirmatory biological evaluation was prompted by the predictive kinetic analysis's further justification of the compounds as potential hit molecules through molecular dynamics (MD) with the variable analyzed pointing out the stability of the complexes.

To determine the pharmacokinetics of meloxicam in the nursehound shark (Scyliorhinus stellaris) during multiple dose administration. Prospective experimental trial. A total of eight clinically healthy adult nursehounds (four males, four females). Meloxicam was administered intramuscularly at a dose of 1.5 mg kg–1 once daily for 7 days. Blood samples were collected from the caudal vein for pharmacokinetic analysis at 2.5 hours and 24 hours after drug administration. After a 4 week washout period, meloxicam was administered orally at the same dose at 12 hour intervals for three repeated doses. Blood samples were collected at 1, 2, 4, 6, 8, 12, 24, 36 and 48 hours after the first administration. Sharks were visually monitored during each study and 4 weeks afterwards for side effects or signs of toxicity. Time required to achieve steady state was assessed by visual inspection and statistical comparison of peak and trough concentrations using a Friedman test; comparison between sexes was performed using a Mann–Whitney U test and p -value was set at 0.05. No animal died or showed clinical signs of toxicity during the study. Meloxicam administered orally did not produce detectable concentrations in plasma. After intramuscular administration, steady state was achieved after five doses, and mean trough and peak plasma concentrations at steady state were 1.76 ± 0.21 μg mL–1 and 3.02 ± 0.23 μg mL–1, respectively. Mean peak concentration accumulation ratio was 2.50 ± 0.22. This study shows that intramuscular posology produces plasma concentrations considered therapeutic for other species. However, meloxicam was not detected in plasma after oral administration. These results suggest that meloxicam administered intramuscularly may be a useful non-steroid anti-inflammatory drug in nursehound sharks. Further pharmacodynamic studies are needed to fully evaluate its clinical use in this species. [ABSTRACT FROM AUTHOR]

Biodegradable polymeric blends are used to study the controlled release of Hydroxychloroquine sulphate (HCQ) as the model drug used extensively in COVID-19 treatments. HCQ drug is loaded in sodium alginate (NaAlg) and lignosulphonic acid (NaLS) blends as matrix are crosslinked using calcium chloride solution. Its release is evaluated in different pH mediums of simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The HCQ release data obtained during experimentation is used to study kinetics using different models to investigate polymeric relaxation's drug diffusion and mechanism in water-soluble HCQ drug. The drug release mechanism best fits the Higuchi model with Fickian diffusion as the primary polymeric relaxation mechanism. [ABSTRACT FROM AUTHOR]

The therapy database currently used in elasmobranchs is still mostly based on empirical data, and there are few efficacy and safety studies supporting clinical practice. In this study, meloxicam pharmacokinetics (PK) were evaluated after a single 1.5 mg/kg IM administration to a group of seven clinically healthy adult undulate skates (Raja undulata Lacepède, 1802). Blood samples were collected before administration and at 15, 30, 60 and 90 min and 2, 4, 8, 12, 24 and 48 h after the IM injection. The meloxicam concentrations in plasma were determined using high-performance liquid chromatography, and PK parameters were calculated using a non-compartmental model approach. The mean ± SEM values of the main PK values were 1.84 ± 0.31 μg/mL for peak plasma concentration, 1.5 ± 0.24 h for time to maximum plasma concentration, 11.43 ± 2.04 h·µg/mL for area under the plasma concentration vs. time curve, 3.55 ± 0.65 h for elimination half-life, and 5.37 ± 0.94 h for mean residency time. No adverse reactions were detected. The relatively high plasma concentration and short time to maximum plasma concentration suggest that meloxicam could turn into an efficient analgesic and anti-inflammatory candidate drug to be used in skates. Further efficacy, pharmacodynamic, and multiple-dose studies with meloxicam are needed in elasmobranchs. [ABSTRACT FROM AUTHOR]

ECMO/ECLS is now a days very common modality for saving patient life in ICU. ECMO is unphysiological circulation which hampers the multiorgan function. Direct impact by releasing of pro-inflammatory cytokinin leads to impact on the many organ homeostasis. The anaesthetist/intensivist must have enough knowledge of pKa/Pd and most importantly still we do not have ideal guidelines for drug dosing. [ABSTRACT FROM AUTHOR]

Copyright of Hungarian Journal of Anesthesiolog & Intensive Therapy / Aneszteziológia és Intenzív Terápia is the property of Hungarian Society of Anaesthesiology & Intensive Therapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The blood-brain barrier (BBB) is composed of four cell populations, brain endothelial cells (BECs), pericytes, neurons, and astrocytes. Its role is to precisely regulate the microenvironment of the brain through selective substance crossing. Here we generated an in vitro model of the BBB by differentiating human induced pluripotent stem cells (hiPSCs) into all four populations. When the four hiPSC-derived populations were co-cultured, endothelial cells (ECs) were endowed with features consistent with BECs, including a high expression of nutrient transporters (CAT3, MFSD2A) and efflux transporters (ABCA1, BCRP, PGP, MRP5), and strong barrier function based on tight junctions. Neuron-derived Dll1, which activates Notch signaling in ECs, was essential for the BEC specification. We performed in vitro BBB permeability tests and assessed ten clinical drugs by nanoLC-MS/MS, finding a good correlation with the BBB permeability reported in previous cases. This technology should be useful for research on human BBB physiology, pathology, and drug development.

Time-resolved analysis assays of receptor-ligand interactions are fundamental in basic research and drug discovery. Adequate methods are well developed for the analysis of recombinant proteins such as antibody-antigen interactions. However, assays for time-resolved ligand-binding processes on living cells are still rare, in particular within microbiology. In this report, the real-time cell-binding assay (RT-CBA) technology LigandTracer®, originally designed for mammalian cell culture, was extended to cover Gram-positive and Gram-negative bacteria. This required the development of new immobilization methods for bacteria, since LigandTracer depends on cells being firmly attached to a Petri dish. The evaluated Escherichia coli CJ236 and BL21 as well as Staphylococcus carnosus TM300 strains were immobilized to plastic Petri dishes using antibody capture, allowing us to depict kinetic binding traces of fluorescently labeled antibodies directed against surface-displayed bacterial proteins for as long as 10-15 h. Interaction parameters, such as the affinity and kinetic constants, could be estimated with high precision (coefficient of variation 9-44%) and the bacteria stayed viable for at least 16 h. The other tested attachment protocols were inferior to the antibody capture approach. Our attachment protocol is generic and could potentially also be applied to other assays and purposes. [ABSTRACT FROM AUTHOR]

Introduction Measuring unlabeled ligand receptor binding kinetics is valuable in optimizing and understanding drug action. Unfortunately, deriving equations for estimating kinetic parameters is challenging because it involves calculus; integration can be a frustrating barrier to the pharmacologist seeking to measure simple rate parameters. Here, a well-known tool for simplifying the derivation, the Laplace transform, is applied to models of receptor-ligand interaction. The method transforms differential equations to a form in which simple algebra can be applied to solve for the variable of interest, for example the concentration of ligand-bound receptor. Methods The goal is to provide instruction using familiar examples, to enable investigators familiar with handling equilibrium binding equations to derive kinetic equations for receptor-ligand interaction. First, the Laplace transform is used to derive the equations for association and dissociation of labeled ligand binding. Next, its use for unlabeled ligand kinetic equations is exemplified by a full derivation of the kinetics of competitive binding equation. Finally, new unlabeled ligand equations are derived using the Laplace transform. These equations incorporate a pre-incubation step with unlabeled or labeled ligand. Results Four equations for measuring unlabeled ligand kinetics were compared and the two new equations verified by comparison with numerical solution. Importantly, the equations have not been verified with experimental data because no such experiments are evident in the literature. Equations were formatted for use in the curve-fitting program GraphPad Prism 6.0 and fitted to simulated data. Discussion This description of the Laplace transform method will enable pharmacologists to derive kinetic equations for their model or experimental paradigm under study. Application of the transform will expand the set of equations available for the pharmacologist to measure unlabeled ligand binding kinetics, and for other time-dependent pharmacological activities. [ABSTRACT FROM AUTHOR]

Kinetic and thermodynamic studies of ligand-receptor interactions are essential for increasing the understanding of receptor activation mechanisms and drug behavior. The characterization of molecular interactions on living cells in real-time goes beyond most current binding assays, and provides valuable information about the dynamics and underlying mechanism of the molecules in a living system. The effect of temperature on interactions in cell-based assays is, however, rarely discussed. In the present study, the effect of temperature on binding of monoclonal antibodies, cetuximab and pertuzumab to specific receptors on living cancer cells was evaluated, and the affinity and kinetics of the interactions were estimated at selected key temperatures. Changes in the behavior of the interactions, particularly in the on- and off-rates were observed, leading to greatly extended time to reach the equilibrium at 21°C compared with at 37°C. However, the observed changes in kinetic characteristics were less than a factor of 10. It was concluded that it is possible to conduct real-time measurements with living cells at different temperatures, and demonstrated that influences of the ambient temperature on the interaction behavior are likely to be less than one order of magnitude. [ABSTRACT FROM AUTHOR]

Designing a multifunctional nanomaterial is always considered as a biggest concern in the field of nanomedicine which aims to promote versatile action in a single use from tracking to therapeutics. Therefore, metallic nanoparticles are well exploited as a major platform with the assemblage of surface modifications which can be effectively engaged for plenty of applications. Here, in this work, we have successfully amalgamated gold coated magnetite core-shell nanoparticles along with bio-functionalization of folic acid and doxorubicin to explore its possibility as a distinct nanocargo for cancer nanotheranostics. This unique combination of both magnetic and optical properties makes its function to be more precise. For example, in case of in-vitro drug-release studies more than 75% of drug moieties are released at acidic pH 5.4 and exactly fitting in first order rate kinetics. As gold shell retains the superparamagnetic nature of the core it exhibited high r 2 values, and because of large relaxivities (r 2 /r 1 ) ratio, they are confirmed as T 2 -weighted contrast agent by MRI. Finally, under microwave of 2.45 GHz exhibited enough heat which can induce both apoptosis & necrosis leading to cell death. Thus, we conclude that our nanoparticle can be a multitool for diagnosis and therapeutics for various human diseases. [ABSTRACT FROM AUTHOR]

Progress made in understanding pharmacokinetic behaviour and pharmacodynamic mechanisms of drug action/resistance has allowed deep insights into the pharmacology of the main chemical classes, including some of the few recently discovered anthelmintics. The integration of pharmaco-parasitological research approaches has contributed considerably to the optimization of drug activity, which is relevant to preserve existing and novel active compounds for parasite control in livestock. A remarkable amount of pharmacology-based knowledge has been generated using the sheep abomasal nematode Haemonchus contortus as a model. Relevant fundamental information on the relationship among drug influx/efflux balance (accumulation), biotransformation/detoxification and pharmacological effects in parasitic nematodes for the most traditional anthelmintic chemical families has been obtained by exploiting the advantages of working with H. contortus under in vitro, ex vivo and in vivo experimental conditions. The scientific contributions to the pharmacology of anthelmintic drugs based on the use of H. contortus as a model nematode are summarized in the present chapter. [ABSTRACT FROM AUTHOR]

Objective: Fenofibrate (FNF), an anti-hyperlipidemic agent, suffers from poor water solubility (0.000707mg/ml) and belongs to class II drug as per BCS, shows a slow dissolution rate. The current investigation aimed to fabricate a fast-dissolving tablet of FNF (not available in the commercial market) using solid dispersion technique employing Vitamin E-D-α-Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) as molecular biomaterial to enhance dissolution rate and reduce the time required to reach the systemic circulation., Materials and Methods: Firstly, carrier material was selected based on the release study via preparing solid dispersion using the melting method, and prepared solid dispersion was characterized. Secondly, fast-dissolving tablets from solid dispersion were fabricated using the direct compression tool and characterized for X-ray diffraction (XRD) pattern, friability, hardness, content uniformity, weight variation and in vitro disintegration test., Results: The X-ray diffraction study confirmed the successful formation of solid dispersion using vitamin E TPGS by analyzing the change in physical state. The fabricated solid dispersion exhibited higher drug content than a physical mixture of FNF. An excipient interference study was also performed in methanol and 0.75% w/v sodium lauryl sulphate. It revealed no significant alterations in the absorption peak of FNF as analyzed using UV spectroscopy at 287nm. In addition, water absorption ratio phase solubility and wetting time were also assessed. In -vitro release of FNF from developed tablets was found significantly higher (93.23%±3.11; p<0.001) as compared to prepared compressed tablet of pure FNF (12.21±2.34%). The dissolution rate was also determined, and data were then kept to various kinetic models such as zero-order chemical kinetic, first-order chemical kinetic, Hixon-Crowell and Higuchi chemical kinetic., Conclusion: A complete and sequential in vitro and physicochemical characterization of developed formulation was carried out to set-up improved and effective treatment for high blood cholesterol., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: A novel inhalation-driven multidose dry powder inhaler (MDPI) that eliminates the need for the patient to coordinate device actuation with inhalation has been developed for delivery of inhaled asthma medications. Objective: To characterize the pharmacokinetics of single-dose fluticasone propionate (Fp) MDPI compared with single doses of Fp dry powder inhaler (DPI) and a metered-dose inhaler (MDI) in healthy subjects. Methods: This was a single-center, open-label, randomized, three-period crossover, single-dose pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized to one of six treatment sequences that contained three treatment arms: Fp MDPI 400 μg/inhalation × two inhalations (800 μg total dose); Fp DPI 250 μg/inhalation × four (1000 μg total dose); and Fp MDI 220 μg/inhalation × four (880 μg total dose). Pharmacokinetics (area under concentration-versus-time curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life [t½]), safety, and tolerability were assessed for each treatment. Results: Plasma Fp concentration-versus-time curves were comparable across treatments. Geometric mean AUC0-t and Cmax for Fp MDPI 800 μg were 19% and 18% higher, respectively, compared with Fp DPI 1000 μg, and 47% and 82% higher, respectively, compared with Fp MDI 880 μg. Median tmax (60.0-60.6 minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three treatments. Single-dose Fp was well tolerated, with no new safety issues noted. Conclusion: Single-dose administration of Fp MDPI 800 μg produced systemic exposure comparable with those for Fp DPI 1000 μg and Fp MDI 880 μg. [ABSTRACT FROM AUTHOR]

A simple kinetic and thermodynamic study of spectrophotometric method for the quantitative analysis of adrenaline (AD) in pure and pharmaceutical dosage forms has been performed. The method is based on the formation of a sensitive green complex between ferrous ion (resulting from the redox reaction between AD and ferric chloride) and nitroso-R-salt reagent (NRS). The increase in absorbance of the colored complex is followed spectrophotometrically at 712 nm as a function of time. The initial rate and fixed time techniques were adopted for constructing the calibration curves. The linearity ranges were found to be 0.5 - 10 and 0.1 - 8 μg·mL for the initial rate and fixed time methods, respectively. Thermodynamic parameters, including the free energy change, enthalpy of formation, and entropy were determined for the reaction product. The method was applied successfully for the estimation of AD in commercial dosage forms with results in a good agreement with those obtained by the official method. [ABSTRACT FROM AUTHOR]

Abstract: A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures. Initial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration–time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted. [Copyright &y& Elsevier]

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible. [ABSTRACT FROM AUTHOR]

Pulse transit time (PTT) is the duration in which a pulse wave travels between two arterial sites within the same cardiac cycle. The aim of our study is to use PTT to examine propofol's effects on the vascular system. Methods. We collected data from 50 healthy women, between 28 and 51 years old, who underwent gynaecological surgery under general anaesthesia. The general anaesthesia was induced with propofol injection (2 mg/kg). PTT measurements were obtained from the R-wave of electrocardiogram and the pulse wave of photoplethysmograph. Two PTT values were obtained; one before (the control) and the other after propofol injection. The results were analysed by Student's t-test. Results. After propofol injection, the PTT was prolonged. The change in the PTT value from that of baseline was significant statistically (P < 0.05, by Student's t-test). The PTT change over time correlated with the degree of vasodilatation over time. Monitoring of PTT not only revealed the magnitude of vascular changes but also demonstrated the onset of vascular dilation, its peak and duration. We conclude that PTT is a useful guide in monitoring the drug kinetics of propofol. [ABSTRACT FROM AUTHOR]

Abstract: A compartmental model for the in vitro uptake kinetics of the anti-cancer agent topotecan (TPT) has been extended from a previously published model. The extended model describes the drug activity and delivery of the pharmacologically active form to the DNA target as well as the catalysis of the aldehyde dehydrogenase (ALDH) enzyme and the elimination of drug from the cytoplasm via the efflux pump. Verification of the proposed model is achieved using scanning-laser microscopy data from live human breast cancer cells. Before estimating the unknown model parameters from the experimental in vitro data it is essential to determine parameter uniqueness (or otherwise) from this imposed output structure. This is formally performed as a structural identifiability analysis, which demonstrates that all of the unknown model parameters are uniquely determined by the output structure corresponding to the experiment. [Copyright &y& Elsevier]

Abstract: A mathematical model for the pharmacokinetics of Hoechst 33342 following administration into a culture medium containing a population of transfected cells (HEK293 hBCRP) with a potent breast cancer resistance protein inhibitor, Fumitremorgin C (FTC), present is described. FTC is reported to almost completely annul resistance mediated by BCRP in vitro. This non-linear compartmental model has seven macroscopic sub-units, with 14 rate parameters. It describes the relationship between the concentration of Hoechst 33342 and FTC, initially spiked in the medium, and the observed change in fluorescence due to Hoechst 33342 binding to DNA. Structural identifiability analysis has been performed using two methods, one based on the similarity transformation/exhaustive modelling approach and the other based on the differential algebra approach. The analyses demonstrated that all models derived are uniquely identifiable for the experiments/observations available. A kinetic modelling software package, namely FACSIMILE (MPCA Software, UK), was used for parameter fitting and to obtain numerical solutions for the system equations. Model fits gave very good agreement with in vitro data provided by AstraZeneca across a variety of experimental scenarios. [Copyright &y& Elsevier]

The insults sustained by transplanted livers (hepatectomy, hypothermic preservation, and normothermic reperfusion) could compromise hepatic function. Hydrogen sulfide (HS) is a physiologic gaseous signaling molecule, like nitric oxide (NO) and carbon monoxide (CO). We examined the effect of diallyl disulfide as a HS donor during hypothermic preservation and reperfusion on intrahepatic resistance (IVR), lactate dehydrogenase (LDH) release, bile production, oxygen consumption, bromosulfophthalein (BSP) depuration and histology in an isolated perfused rat liver model (IPRL), after 48 h of hypothermic storage (4°C) in University of Wisconsin solution (UW, Viaspan). Livers were retrieved from male Wistar rats. Three experimental groups were analyzed: Control group (CON): IPRL was performed after surgery; UW: IPRL was performed in livers preserved (48 h-4°C) in UW; and UWS: IPRL was performed in livers preserved (48 h-4°C) in UW in the presence of 3.4 mM diallyl disulfide. Hypothermic preservation injuries were manifested at reperfusion by a slight increment in IHR and LDH release compared with the control group. Also, bile production for the control group (1.32 µL/min/g of liver) seemed to be diminished after preservation by 73% in UW and 69% in UW HS group at the end of normothermic reperfusion. Liver samples analyzed by hematoxylin/eosin clearly showed the deleterious effect of cold storage process, partially reversed (dilated sinusoids and vacuolization attenuation) by the addition of a HS delivery compound to the preservation solution. Hepatic clearance (HC) of BSP was affected by cold storage of livers, but there were no noticeable differences between livers preserved with or without diallyl disulfide. Meanwhile, livers preserved in the presence of HS donor showed an enhanced capacity for BSP uptake (kCON = 0.29 min; kUW = 0.29 min; kUWS = 0.36 min). In summary, our animal model suggests that hepatic hypothermic preservation for transplantation affects liver function and hepatic depuration of BSP, and implies that the inclusion of an HS donor during hypothermic preservation could improve standard methods of preparing livers for transplant. [ABSTRACT FROM AUTHOR]

Abstract: Epidural fat provides sufficient cushion for the pulsatile movements of the dural sac, protects nerve structures, facilitates the movement of the dural sac over the periosteum of the spinal column during flexion and extension, and forms a pharmacologic reservoir of lipophilic substances. Root cuffs have a cellular component that affects the passage of substances injected epiduraly or near the intervertebral foramen, depending on the site of injection, preganglionar, postganglionar or ganglionar. We found fat inside root cuffs but not within the dural sac. Fat in this location may have affect kinetics of lipophilic drugs injected near nerve root cuffs. Ultrastructural morphology of the cellular component at preganglionar level may help explain unexpected subdural blockade after injection of local anesthetic via transforaminal route. Other morphological aspects of nerve root cuffs help to understand the function of the blood-nerve barrier. Based in this anatomical knowledge, we can speculate on the possible anesthetic implications of epidural fat in terms of the pharmacokinetics of drugs injected into the epidural space and the tasks of locating the epidural space and inserting an epidural catheter during anesthetic procedures. [Copyright &y& Elsevier]

A model describing the response of the growth of single human cells in the absence and presence of the anti-cancer agent topotecan (TPT) is presented. The model includes a novel coupling of both the kinetics of TPT and cell cycle responses to the agent. By linking the models in this way, rather than using separate (disjoint) approaches, it is possible to illustrate how the drug perturbs the cell cycle. The model is compared to experimental in vitro cell cycle response data (comprising single cell descriptors for molecular and behavioural events), showing good qualitative agreement for a range of TPT dose levels. [Copyright &y& Elsevier]

Ultrafiltration (UF) is a filtrate selection method with a wide range of biomedical and clinical applications, including detoxification of blood in hemodialysis and peritoneal dialysis. New is, however, the use of UF as a convenient in vivo sampling method that, for example, has been used in diabetics. Ultrafiltration avoids complicated and time-consuming recovery calculations that are necessary when using in vivo microdialysis, as recoveries of low molecular weight molecules are near 100%. The subcutaneously or intravenously placed UF probes have been studied for off-line sample analysis and for continuous on-line monitoring, in a wide variety of species, including dogs, rats, pigs and humans.This review discusses the potential of in vivo UF as a continuous tissue sampling technique in clinical research areas, and in several major biomedical applications including glucose and lactate monitoring and drug kinetic studies. [Copyright &y& Elsevier]

Barbiturate coma is initiated in brain-injured patients whenever elevated intracranial pressure remains unresponsive to other therapeutical strategies. However, barbiturates alter cortical activity resulting in difficulties in clinical evaluation. Therefore, we investigated the impact of long-term thiopental administration on responsiveness to exteroceptive stimuli in relation to pharmacokinetics of thiopental in CSF and serum. Long-term infusion increases thiopental levels which remain elevated for 6 and 9 days in CSF and serum, respectively, after termination of its administration. Prolonged unresponsiveness to exteroceptive stimuli correlates with persisting thiopental in CSF and serum. Thus, quantitative analysis of thiopental in serum becomes indispensable in predicting the length of drug-induced neurological impairment and in avoiding misinterpretation of the neurological status. [ABSTRACT FROM AUTHOR]