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.     

PERCHLOROETHYLENE EXTRACTION DESULFURIZATION OF LOW SULFATE COALS

The perchloroethylene coal refining process utilizes perchloroethylene (PCE) as its solvent in all phases of the precombustion desulfurization process, including wet grinding, organic sulfur removal, gravitational separation of pyrites and mineral matter, and recovery of elemental sulfur (S₈). The Process is capable of producing compliance coal which emits less than 1.2 lb SO_X/MBTU when burnt, starting from 5 mass percent sulfur Midwestern and Eastern U.S. coals. However, the process efficiency was found to be very strongly dependent upon the degree of weathering or the level of coal oxidation. In this paper, perchloroethylene extraction data of fresh, low-sulfate coals are summarized and critically assessed. The extraction efficiency of the organic sulfur removal ranged from 5 to 30 percent for fresh coals, while that for weathered coals ranged from 30 to 60 percent. This study provides a valuable insight into the chemical reaction mechanism of perchloroethylene desulfurization process.     

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.     

The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy

BACKGROUND: The effect of topical corticosteroids after excimer laser photorefractive keratectomy (PRK) remains a matter of some controversy. Refractive effects may be different according to the amount of myopia and timing of instillation. METHODS: Two groups of patients were studied: Study A consisted of 215 eyes (128 patients) with PRK (mean baseline myopia, -6.53 +/- 2.22 D) that received no corticosteroids (No Corticosteroid Group) unless significant regression or corneal haze appeared (Delayed Corticosteroid Group), and in Study B, we randomly assigned eyes to the Initial Corticosteroid Group (mean baseline myopia, -6.39 +/- 1.84 D) or the No/delayed Corticosteroid Group (mean baseline myopia -5.78 +/- 2.02 D). Clinical results after PRK for low-to-moderate and high myopia were compared. RESULTS: In the first group, 70.9% (73 eyes) of moderately myopic eyes (mean, -4.56 +/- 1.10 D) belonged to the No Corticosteroid Group that had a mean refraction of -5.39 +/- 1.77 D. Delayed Corticosteroid Group eyes were more myopic (mean, -7.52 +/- 2.10 D), and showed more severe haze than those in the No Corticosteroid Group. In study B, only in high myopes with more than -6.00 D (mean, -7.76 +/- 1.15 D) did refraction and corneal haze outcomes show significant difference between the Initial Corticosteroid Group and the No/delayed Corticosteroid Group. CONCLUSIONS: The effects of topical corticosteroids after PRK were less in moderate myopes compared to high myopes. Delayed instillation of corticosteroids did not reverse the regression or haze whereas initial instillation showed a beneficial effect on high myopes but not on moderate myopes.