Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain due to cancer or cancer therapy.

Oral mucositis is a treatment limiting toxicity of cancer therapy. The purpose of this study was to assess the impact of doxepin oral rinse in the management of oral mucosal pain in cancer patients. Forty-one cancer patients with oral mucosal pain were provided a solution of doxepin (0.5%) for oral rinsing. Oral pain was assessed prior to rinsing, and following rinsing for 4 h using a visual analogue scale (VAS). Adverse effects were recorded. Doxepin rinse resulted in a reduction of pain intensity of more than 50%, with pain relief extending for more than 3 h with pain not returning to baseline 4 h after rinsing. The rinse was tolerated by patients with mucosal damage, and had acceptable taste, and infrequent mucosal stinging with use. Some patients reported sedation after use, likely due to systemic absorption. The results of this single dose trial suggest that topical doxepin rinse has significant ability to provide clinically significant pain relief in patients with mucosal damage with an extended duration of effect.

Food and nutritional care in hospitals: how to prevent undernutrition--report and guidelines from the Council of Europe.

In 1999 the Council of Europe decided to collect information regarding Nutrition programmes in hospitals and for this purpose a network consisting of national experts from eight of the Partial Agreement member states was established. The aim was to review the current practice in Europe regarding hospital food provision, to highlight deficiencies and to issue guidelines to improve the nutritional care and support of hospitalized patients. Five major problems seemed to be common in this context: 1) lack of clearly defined responsibilities; 2) lack of sufficient education; 3) lack of influence of the patients; 4) lack of co-operation among all staff groups; and 5) lack of involvement from the hospital management. To solve the problems highlighted, a combined 'team-effort' is needed from national authorities and all staff involved in the nutritional care and support, including hospital managers.

Molecular basis for prostaglandin potency. III. Tests of the significance of the "hairpin conformation" in biorecognition phenomena.

Prostaglandin analogs of the PGF2 alpha, 15-epi-PGF2 alpha, and PGE2 type bearing the following methyl substitution patterns -- 15-Me, 16, 16-(Me)2, 17, 17-(Me)2, and 18, 18, 20-(Me)3 -- and analogs constrained to "hairpin" alignment [via 1, (omega-1)-olide formation] and to "non-hairpin" arrangements [via 1, 9- and 1, 15-olide formation] are compared in the following biological assays: contraction of uterine and gastro-intestinal smooth muscle strips, luteolytic antifertility potency in the hamster, binding affinity to two different PGF2 alpha-receptor preparations from bovine corpora lutea, binding to the PGE-specific receptors from rat kidney and liver, inhibition of ADP- induced aggregation of human platelet-rich-plasma, and the effect on rat blood blood pressure. The methylated prostaglandins were also concerted to the corresponding prostacyclins and examined as to action on the platelet and on rat blood pressure. All evidence points to topographically distinct receptors for F2 alpha-, E- and I2- type prostaglandins. Cross-reactivity is reduced in most of the analogs examined. Independent of the target organ or tissue, the receptors show common features based on the functional class of PG recognized. "Hairpin" alignment improves binding (and potency) only for the PGF2 alpha specific assays. PGE-specific binding and potency is disrupted to an increasing extent as the chain branching point is moved further from the 15-hydroxyl center. In contrast 16, 16-dimethylation is particularly disruptive for the PGI2/E1 platelet receptor interaction.

Evidence for a PGE-receptor in the rat kidney.

A membrane preparation derived from homogenates of the rat kidney has been shown to possess a high affinity for prostaglandins of the E-series. Other prostaglandins including PGI2 had characteristic but significantly weaker binding properties. A 15-hydroxyprostaglandin dehydrogenase (PGDH) was found to be associated with the membrane fraction studied. However it was possible to distinguish between this and the "receptor" binding by kinetic studies and by the use of a new inhibitor highly specific for PGDH.

A 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin A in rabbit kidney.

Examination of a soluble fraction derived from homogenates of rabbit kidney papilla revealed the existence of a 15-hydroxyprostaglandin dehydrogenase specific for A-type prostaglandins. Prostaglandins of the E- and F-series were not substrates for this enzyme. In agreement with published data, the 15-hydroxyprostaglandin dehydrogenase(s) derived from the kidney cortex were found to degrade all prostaglandins examined (PGE, PGF, PGA) in the presence of added cofactor NAD. Thus it is evident that in this species the kidney 15-hydroxyprostaglandin dehydrogenases are anatomically compartmentalized so that the papilla is able to metabpable of degrading E-, F-, and A-type prostaglandins by this metabolic pathway.

The reaction of PGA1 with sulfhydryl groups; a component in the binding of A-type prostaglandins to proteins.

Prostaglandins of the A-type (PGAs) were found to react with cysteine or reduced glutathione to yield water-soluble adducts, an effect due to a reaction of the sulfhydryl group of cysteine with the unsaturated carbonyl function of these prostaglandins. The binding of tritiated PGA1 to the supernatant fraction of rabbit papilla homogenates reported by Attallah and Lee (4) appears to be related to this phenomenon since ethacrynic acid, a compound also highly reactive with the thiol group of cysteine, effectively competes with PGAs for the binding site in this soluble kidney preparation. Evidence is also presented to show that this binding of PGAs to the "acceptor' of the rabbit kidney is related to an interaction with a thiol group of 15-hydroxy prostaglandin dehydrogenase, the enzyme chiefly involved in the metabolism of prostaglandins.

Structural requirements for the binding of prostaglandins.

The binding of prostaglandins and analogs to the lipocyte PGE receptor was shown to exhibit a high degree of structural specificity. Small changes, particulary at the 9-keto or 15-hydroxyl position, were found to drastically diminish interaction with the receptor. Studies of a rather substantial number of compounds revealed a close relationshio between affinity for the lipocyte PGE receptor and the ability to stimulate cyclic AMP synthesis in the isolated mouse ovary. In general, activities in these two parameters follow the biological potencies generally recognized for the compounds.

Metabolism of imidazole by a pseudomonad.

Intermediates formed during the microbial degradation of imidazole, namely 4(5)-imidazolone, formiminoglycine, and possibly glycine, are similar to those formed during metabolism of imidazole derivatives.