The current situation of hereditary angioedema patients in Germany: results of an online survey.

Introduction: Hereditary angioedema (HAE) is a rare hereditary disease with an estimated prevalence of approximately 1 in 50,000. Methods: An online survey was performed between January and June 2021 on a total of 99 HAE patients (with 92 of them aged 15 years and older and 7 of them being parents of patients under the age of 15 years). They were asked about their current situation, with a focus on the disease. Results: The survey results show that HAE has a strong influence on the patients' quality of life. In particular, the anxiety and uncertainty of not knowing when a swelling attack will occur is considered burdensome by the patients. In addition, there can be physical problems during an attack (depending on its severity) that severely burden and limit patients in their everyday lives. Only one-third of the patients surveyed stated that no or only very minor physical limitations occurred during their most recent swelling attack. Almost three-quarters of all patients receive regular treatment at an HAE center. The patients are mostly satisfied with the therapy and particularly with long-term prophylactics (LTPs). When an LTP was used, the frequency and severity of the swelling attacks, and their duration, were significantly lower and/or shorter than when no LTP was used. Discussion: Despite the high level of satisfaction with their current medication, 62% of patients expressed a strong/very strong interest in an oral LTP. In the group of patients already using an LTP, 74% reported a strong/very strong interest in an oral medication for long-term prophylaxis. The simplicity and minimal time involved in LTP use are considered beneficial to patients' quality of life.

Synthesis and evaluation of long-acting D-penicillamine derivatives.

This study extends the use of two lathyrogens, ss-aminopropionitrile (BAPN) and D-penicillamine (DPA) from daily systemic or local-topical administration to long-time acting agents. This was achieved by converting the hydrophilic drugs into lipophilic derivatives. The synthesis of functional derivatives of DPA consisted in esterification with methyl-, hexyl-, or benzyl alcohols in the presence of thionylchloride. The esters formed were hydrochlorides, acidic and soluble in water. During neutralization in vitro or in vivo by tissue fluid, an oily substance is formed that elutes from a hydrogel polymer at a much slower rate than hydroplilic DPA itself. The degree of lipophilicity, measured as a partition coefficient between octanol/water, was highest for hexyl ester and lowest for methyl ester DPA. A single injection of either DPA hexyl ester HCl or 3-hexyl(amino) propionitrile into the full thickness skin incision wound in rats significantly lowered the breaking strength of the wound 12 days after injection, indicating the interference with collagen cross-linking. Both agents injected into the breast adenocarcinoma in Fisher rats significantly inhibited tumor growth without any signs of local or systemic toxicity. We conclude that these lipophilic lathyrogens with prolonged effectiveness are suitable in the treatment of pathologies, consisting of excessively cross-linked or deposited collagen (fibrotic adhesions, strictures, stenosis, and scar contractures) and in the treatment of single, solitary tumors, malignant and benign.

Cold and cryopreservation of monkey liver slices.

Both cynomolgus and rhesus monkeys are utilized in chemical toxicity screening and drug development studies by industry and government laboratories. Along with better utilization of their tissue for in vivo studies, it would be advantageous if the tissue could be cold-preserved or cryopreserved for future in vitro experimentation. Therefore, livers were excised from control monkeys and precision-cut tissue slices were prepared. The objective of this study was twofold: to compare cold-preservation solutions (V-7 and Viaspan) and to compare controlled-rate and vitrification cryopreservation protocols. Monkey liver slices were cold-stored in V-7 or Viaspan preservation solutions for 7 days. V-7 maintained slice viability for 5 days whereas Viaspan maintained slice viability for 1 day. In the controlled-rate freezing procedure, slices were exposed to 10% dimethyl sulfoxide and 90% fetal calf serum (FCS); cooled at the rate of 0.5 degrees C, 1 degrees C, or 12 degrees C per min to -70 degrees C; then placed into liquid nitrogen. Vitrification was accomplished by exposing slices stepwise to increasing concentrations of 1,2-propanediol (1.2, 2.4, and 4 M) in FCS with direct submersion into liquid nitrogen. In both protocols, slices were rewarmed quickly to 37 degrees C and then incubated in FCS for 4 h. Three viability parameters were used to measure slice viability - retention of potassium, leakage of lactate dehydrogenase, and synthesis of protein. Liver slices cryopreserved at a rate of 0.5 degrees C per min and vitrified successfully retained 80 to 90% of their viability. These results confirm the feasibility of functional cold preservation and cryopreservation protocols for monkey liver slices that would allow for a more efficient use of monkey tissue.