[Amputation and prosthesis attachment of the lower extremities]. / Amputation und Prothesenversorgung der unteren Extremität.

Approximately 61,000 amputations are performed in Germany per year. In most cases the lower limbs are affected. The reasons for amputations are arteriosclerosis, diabetes mellitus, severe infections, tumors and complex trauma to the extremities. A decision must be made concerning whether a salvage procedure or amputation is appropriate, specially after trauma. In cases where the need for amputation is clear, the site of amputation needs to be planned in advance with the aim of creating a stump which allows sufficient prosthetic attachment. Adjuvant pain therapy is mandatory, especially in order to avoid subsequent phantom pain. The type of prosthetic restoration is influenced by the grade of mobility and personal requirements of patients. Moreover, aftercare and adjusted rehabilitation are recommended.

[Mucus models for investigation of intestinal absorption mechanisms. 4. Comparison of mucus models with absorption models in vivo and in situ for prediction of intestinal drug absorption]. / Muscusmodelle zur Untersuchung von intestinalen Absorptionsmechanismen. 4. Mitteilung: Vergleich des Mucusmodells mit Absorptionsmodellen in vivo and in situ zur Vorhersage intestinaler Wirkstoffabsorption.

Intestinal absorption with an in vitro model using pig intestinal mucus was examined by means of in vivo and in situ experiments in the rat. With 10 compounds of different structure, in vitro, in situ, and in vivo models were tested. The in vitro model in the present form can only simulate the first step of intestinal absorption, namely diffusion through the mucus layer. Indeed, we found that one function of the intestinal mucus can be described being a molecular sieve with a molecular mass (MM) cut off within the range of about 600 to 700 [g/mol]. Absorption of substances with higher molecular mass remains at a low level. With the mucus model prediction of intestinal absorption of hydrophilic substances with MM < 600 to 700 [g/mol] will be possible, if the mass transport in the mucus layer is rate limiting. Independent of polarity, it is also valid for substances of MM > 600 to 700 [g/mol]. Estimation however, is not valid for lipophilic substances and MM < 600 to 700 [g/mol], when mass transport from the mucus to the adjacent compartments is rate limiting. Further optimization of the mucus model for a more extensive application seems possible and reasonable with respect to saving in vivo experiments with animals.

[Mucus models for investigation of intestinal absorption mechanisms. 3. A mathematical simulation model of drug diffusion through enteral mucus]. / Mucusmodelle zur Untersuchung von intestinalen Absorptionsmechanismen. 3. Mitteilung: Ein mathematisches Simulationsmodell der Wirkstoffdiffusion durch enteralen Mucus.

The diffusion of drug substance in a closed three-compartment model through a mucus layer to equilibrium is simulated by available pharmacokinetic programs. The obtained curves conform very well to the values experimentally found. If mucus is replaced by buffer solution an explicit equation from the literature, the method used and the experimental findings give the same results. Examination of the rate constants k1 for the diffusion in, kD through and k2 from the mucus shows the significance of the relation k1/k2 > 1, = 1, < 1 as a measure for the affinity of the active agent to the mucus. The discussion of the kinetic parameters shows, as in previous results, no criterion for assuming specific mucus binding. Because of its unspecifity the usual term "mucus binding" should be replaced by "mucus retention".

[Mucus models for investigation of intestinal absorption mechanisms. 2. Mechanisms of drug interactions with intestinal mucus]. / Mucusmodelle zur Untersuchung von intestinalen Absorptions-mechanismen. 2. Mitteilung: Mechanismen der Wechselwirkung von Wirkstoffen mit Intestinalmucus.

Using in vitro models previously described [1] mucus retention and mucus diffusion of polar and non-polar drugs were measured. It could be shown that drug interaction with pig intestinal mucus was based on non-specific binding. The pH-dependence of retention by mucus does not confirm electrostatic interaction of drugs with mucus but favour drug distribution to hydrophobic areas within the mucus. High lipophilicity and retention by mucus correlate with low diffusion of drugs through mucus.