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The bisphosphonates clodronate and alendronate are drugs in the therapy of osteoporosis or Paget's disease. They are highly hydrophilic and therefore of low oral bioavailability. Determination methods for bisphosphonates are often laborious and expensive equipment is needed. The presented quantification method based on kinetic measurement of the fluorescence decrease of an Al(3+)-morin complex can be used to determine the bisphosphonate content in aqueous and plasma samples. The intra- and inter-assay accuracies were found to be within 98.8% and 102.3% of the target samples for clodronate and within 97.2% and 105.0% of the target samples for alendronate. The LOQ was defined as 15.6 ng/ml for clodronate and 62.5 ng/ml for alendronate. In serum samples, intra- and inter-assay accuracy was found to be within 99.0% and 101.6% of the target samples for clodronate and within 97.8% and 102.6% of the target samples for alendronate. In serum samples, the LOQ was defined as 1.55 mg/ml for clodronate and 0.39 mg/ml for alendronate. Though less sensitive in serum, the presented method could support research on the development of drug delivery systems in vitro and in vivo for the investigated and other structurally related bisphosphonates., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Limitations in therapy induced by adverse effects due to unselective drug availability and therefore the use of potentially too high doses are a common problem. One prominent example for this dilemma are inflammatory diseases. Colloidal carriers allow one to improve delivery of drugs to the site of action and appear promising to overcome this general therapeutic drawback. Specific uptake of nanoparticles by immune-related cells in inflamed barriers offers selective drug targeting to the inflamed tissue. Here we focus on nanocarrier-based drug delivery strategies for the treatment of common inflammatory disorders like rheumatoid arthritis, multiple sclerosis, uveitis or inflammatory bowel disease.

The objectives of this study were to evaluate the specific effect of the ACE-inhibitor lisinopril on myocardial mass and diastolic function in uremic patients using a protocol designed to leave blood pressure unchanged. Nineteen hemodialysis patients (7 males; mean age: 55 +/- 13 years; mean time on dialysis: 44 +/- 35 months) received lisinopril for 6 months in addition to their preexistent antihypertensive treatment regimens (mean: 1.4 +/- 0.8 drugs). Doses of antihypertensive drugs were adjusted to keep both systolic and diastolic blood pressure stable. Nine patients were withdrawn from lisinopril treatment after 43 +/- 33 days because of hypotension (n = 4), withdrawn consent (n = 3), stroke (n = 1) and cough (n = 1). Seven of them were further studied as controls. Ten patients received 6.4 +/- 4 mg lisinopril as a mean for 6 months. Mean myocardial mass, calculated by M-mode echocardiography, was 324 +/- 103 g before, and 313 +/- 79 g after 6 months of lisinopril treatment. In the control patients, myocardial mass was 318 +/- 110 g initially, and after 6 months, it was 334 +/- 159 g. Early and late transmitral diastolic flow velocities were not significantly influenced by lisinopril. Throughout the study, both the systolic and diastolic 24-h mean blood pressure levels remained stable (systolic: before: 145 +/- 19 mmHg, at 6 months: 147 +/- 17 mmHg; diastolic: before: 87 +/- 12 mmHg, at 6 months 87 +/- 10 mmHg). Thus, no specific effect of lisinopril on regression of myocardial hypertrophy or improvement of diastolic function could be observed within a 6-month period in this small group of hemodialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

6-mercaptopurine (MP) conjugates of bovine gamma globulin (BGG) and human serum albumin (HSA) with increasing numbers of MP-groups per protein molecule were prepared and some physicochemical and antigenic properties studied. The electrophoretic mobility increased proportionally to the degree of substitution. In the same manner the formation of high molecular weight aggregates increased. A loss of BGG and HSA specific determinants was observed too. The physicochemical and antigenic properties of these antigen-suppressive agent-conjugates with low and medium coupling degree (to MP26-BGG and MP20-HSA) were similar to the unmodified antigens. The affinity of rabbit anti-DNP-antibodies decreased from K0 = 1,4 - 10(6) M-1 of the unmodified antibodies to 6,5 - 10(5), 3,6 - 10(5) and 3,4 - 10(5) M-1 of the antibodies conjugated with 15, 21 and 29 MP-groups per antibody molecule. The precipitation capacity of the MP-conjugated antibodies decreased to 89, 85 and 61% for the same coupling ratios. These results suggest that the upper limit of the coupling ratio of the antibodies is 20 to 1.