Nonlinear protein binding and enzyme heterogeneity: effects on hepatic drug removal

The kinetics of substrate removal by the liver and the resulting nonlinear changes in unbound fraction along the flow path at varying input drug concentrations were examined by a model simulation study. Specifically, we varied the binding association constant, KA, and the Michaelis-Menten constants (Km and Vmax) to examine the steady state drug removal (expressed as hepatic extraction ratio E) and changes in drug binding for (i) unienzyme systems and (ii) simple, parallel metabolic pathways; zonal metabolic heterogeneity was also added as a variable. At low KA, E declined with increasing input drug concentration, due primarily to saturation of enzymes; only small differences in binding were present across the liver. At high KA, a parabolic profile for E with concentration was observed; changes in unbound fraction between the inlet and the outlet of the liver followed in parallel fashion. Protein binding was the rate-determining step at low input drug concentrations, whereas enzyme saturation was the rate-controlling factor at high input drug concentration. Heterogeneous enzymic distribution modulated changes in unbound fraction within the liver and at the outlet. Despite marked changes in unbound fraction occurring within the liver for different enzymic distributions, the overall transhepatic differences were relatively small. We then investigated the logarithmic average unbound concentration and the length averaged concentration as estimates of substrate concentration in liver in the presence of nonlinear drug binding. Fitting of simulated data, with and without assigned random error (10%), to the Michaelis-Menten equation was performed; fitting was repeated for simulated data obtained with presence of a specific inhibitor of the high-affinity, anteriorly distributed pathway. Results were similar for both concentration terms: accurate estimates were obtained for anterior, high affinity pathways; an overestimation of parameters was observed for the lower affinity posteriorly distributed pathways. Improved estimations were found for posteriorly distributed pathways upon inhibition with specific inhibitors; with added random error, however, the improvement was much decreased. We applied the method for fitting of several sets of metabolic data obtained from rat liver perfusion studies performed with salicylamide (SAM) (i) without and (ii) with the presence of 2,6-dichloro-4-nitrophenol (DCNP), a SAM sulfation inhibitor. The fitted results showed that SAM sulfation was a high-affinity high-capacity pathway; SAM glucuronidation was of lower affinity but comparable capacity as the sulfation pathway, whereas SAM hydroxylation was of lower affinity and lower capacity.     

Clinical risk factors determining recurrence in Crohn''s disease

Absorbable and nonabsorbable buried sutures were studied in primary cleft lip repair. Group 1 (N = 56) consisted of patients repaired with buried nonabsorbable material (monofilament nylon). Group 2 (N = 47) consisted of patients repaired with absorbable materials (polyglyconate, polydioxanone). All patients were monitored for 12 months. There were stitch abscesses in Group 1 (14%). There were no abscesses in Group 2. This difference was significant (p = 0.007). Abscesses were located in the suture line with no identifiable distribution. There was no significant difference in the cosmetic appearance of the scars in Groups 1 and 2. These results support the view that absorbable sutures are preferable to nonabsorbable sutures for primary cleft lip repair.     

Shear horizontal wave propagation in periodically layeredcomposites

The transverse resonance approach to guided wave analysis is applied to shear horizontal (SH) wave propagation in periodically layered composites. It is found for SH waves that at high values of the guided wavevector β, the wave energy is trapped in the slower of the two media and propagates accordingly at the slower wavespeed. At low values of β, however, the modes demonstrate a clustering behavior, indicative of the underlying Floquet wave structure. The number of modes in a cluster is observed to correlate with the number of unit cells in the layered plate. New physical insights into the behavior of these systems are obtained by analyzing the partial waves of the guided SH modes in terms of Floquet waves. We show that the fast and slow shear waves in the periodically layered composite play an analogous role to the longitudinal and shear partial waves comprising Lamb waves in a homogeneous plate     

Decision by the Principle Board of the Polish Allergy Society

A review of isolates of Neisseria meningitidis and other laboratory evidence of meningococcal infection was carried out for the period 1990-1995. Thirty-three patients with evidence of meningococcal disease were identified over the six year period. Group B organisms were the most commonly identified, but an increase in Group C has occurred and is almost equal in number. Data from clinical, laboratory and public health sources should be centralized in a National Surveillance Centre.     

Mean residence time of gas in mechanically agitated gas–liquid contactors

In the present study of gas–liquid contactors, mean residence/contact time was calculated from knowledge of superficial velocity and the gas phase hold-up, for various gas rates and impeller geometry and speeds, and compared with values obtained from RTD measurements. A new correlation, involving Flow Number, Froude Number, system geometry and the physical properties, is proposed. This uses the authors data and those available in literature.     

Flicker noise in gate overlapped polycrystalline silicon thin-filmtransistors

A study of the noise performance of gate overlapped polycrystalline silicon thin-film transistors (TFTs) is presented. Low-frequency noise measurements were carried out on n- and p-type samples fabricated by excimer laser crystallization. It is shown that the carrier number fluctuation model applies not only to n-type but also to p-type devices. The density of oxide traps was extracted from the noise measurements and was of the order of 10¹⁸-10¹⁹ eV^-1 cm^-3     

Capacity-achieving sequences for the erasure channel

This paper starts a systematic study of capacity-achieving (c.a.) sequences of low-density parity-check codes for the erasure channel. We introduce a class A of analytic functions and develop a procedure to obtain degree distributions for the codes. We show various properties of this class which help us to construct new distributions from old ones. We then study certain types of capacity-achieving sequences and introduce new measures for their optimality. For instance, it turns out that the right-regular sequence is c.a. in a much stronger sense than, e.g., the Tornado sequence. This also explains why numerical optimization techniques tend to favor graphs with only one degree of check nodes.