Autoantibodies against zinc transporter 8 further stratify the autoantibody-defined risk for type 1 diabetes in a general population of schoolchildren and have distinctive isoform binding patterns in different forms of autoimmune diabetes: results from the Karlsburg Type 1 Diabetes Risk Study.

AIMS: To evaluate the diagnostic relevance of autoantibodies against zinc transporter 8 (ZnT8) in schoolchildren from the general population as well as in people with autoimmune diabetes. METHODS: A total of 137 schoolchildren positive for at least one of the three major diabetes-associated autoantibodies, without diabetes heredity or preselection on HLA typing, from the Karlsburg Type 1 Diabetes Risk Study, as well as 102 people at type 1 diabetes onset, 88 people with latent autoimmune diabetes in adults and 119 people with type 2 diabetes, were analysed for different ZnT8 autoantibody variants. RESULTS: Zinc transporter 8 autoantibody positivity was found in 18% of autoantibody-positive schoolchildren, with a noticeable association with other autoantibodies associated with type 1 diabetes and disease progression. Furthermore, ZnT8 autoantibody positivity was associated with diabetes progression in schoolchildren positive for autoantibodies against insulinoma-associated antigen-2 (IA-2) and, importantly, in seven IA-2 autoantibody-negative schoolchildren. Additionally, ZnT8 autoantibodies were found in 56% of people with type 1 diabetes, predominantly directed against all three ZnT8 variants and comparable to schoolchildren with multiple autoantibodies. In contrast, ZnT8 autoantibodies were detected in 10% of people with latent autoimmune diabetes in adults, none of them with reactivity to all three isoforms. CONCLUSION: Zinc transporter 8 autoantibodies are useful markers for prediction of type 1 diabetes in a general population, further stratifying the risk of progression in autoantibody-positive children. ZnT8 autoantibodies are also important markers in adult-onset diabetes, with a completely different reaction pattern in type 1 diabetes in comparison to latent autoimmune diabetes in adults, and may therefore help to differentiate between the two forms.

[Studies on the disposition of meproscillarin in rat and dog (author's transl)]. / Untersuchungen zur Disposition von Meproscillarin an den Spezies Ratte und Hund.

The disposition of 14-hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) formed by methylation of proscillaridin was tested in rats and dogs. Meproscillarin is better absorbed than proscillaridin. The drug is primarily eliminated via the bile. After oral administration 6% of the dose were excreted with urine by the rat and 3% by the dog. The main metabolite in the bile was shown to be a glucuronide of meproscillarin.

[Development of an oral retard preparation of verapamil and absorption study in the anesthetized dog]. / Entwicklung einer oralen Retardform von Verapamil und Prüfung der Resorption am narkotisierten Hung

1. An oral retard preparation of verapamil (Isoptin retard) is described. The sustained release of the active compound from verapamil retard is obtained by mixing and pressing verapamil hydrochloride with sodium alginate. The proportion of active compound and physiologically indifferent additive may range between 1:1 and 1:2. 2. The determination of the in vitro release according to the half-change method shows that verapamil is completely released from the retard preparation only after 6 to 7 h; with conventional dragées more than 90% of the compound is dissolved already after 10 min. 3. In artificial gastric and intestinal juice (pH 1.4 and 7.5) similar times of release are found. 4. The in vitro results are supported by tests on the intestinal absorption in the anesthetized dog. In a ligated duodenum section verapamil is, 3 to 8 h after application, markedly more slowly released and absorbed from the retard preparation than from conventional dragées.

Biotransformation of lofexidine in humans.

1. Concentrations of unchanged drug and patterns of radioactive components in urine have been determined by h.p.l.c. following single oral doses of [14C]lofexidine hydrochloride (0.32 mg) to six human subjects. 2. A mean of 12% of the administered dose was excreted in urine as unchanged lofexidine, but the wide range (5-20% dose) indicated significant intersubject variation in the extent of biotransformation. This drug would appear to be metabolized more extensively than the related anti-hypertensive agent, clonidine. 3. The principal metabolite of lofexidine was 2,6-dichlorophenol, which was apparently excreted in urine as two O-glucuronic acid conjugates. The same two metabolites were also the main 14C components circulating in plasma at peak 14C concn. Formation of the phenol from lofexidine probably involved direct O-dealkylation rather than stepwise degradation of the side-chain. 4. Patterns of 3H components in the urine of rats and dogs after oral administration of [3H]lofexidine hydrochloride (0.1 mg/kg) were generally similar to those in human urine.