Introduction: Previous studies demonstrated a continues decline in fetal growth throughout singleton pregnancy after bariatric surgery. However, intrauterine growth in twin pregnancy is subjected to further underlying processes. This study was to investigate the longitudinal assessment of fetal biometry and abdominal fat thickness of twin pregnancies conceived after gastric bypass surgery and compare them to BMI-matched and obese controls. Materials and methods: We retrospectively assessed ultrasound data of 30 women with dichorionic-diamniotic twin pregnancy (11 women after gastric bypass surgery, 9 obese mothers with pregestational BMI ≥ 30 kg/m² and 10 BMI and age matched controls). We assessed fetal growth parameters including fetal subcutaneous adipose tissue thickness (FSCTT) as well as newborn biometry after delivery. Patient characteristics were obtained from the medical records. Results: The rise in FSCTT curves was markedly slower in twin offspring of women with history of gastric bypass as compared to offspring of obese mothers and offspring of BMI matched controls. Hence, FSCTT was significantly decreased in gastric bypass offspring as compared to both control groups at 34 weeks of gestation. Also, growth curves of abdominal circumference were decreased in offspring of gastric bypass patients as compared to obese mothers. Infants of mothers with history of gastric bypass showed significantly lower birth weight percentiles compared to newborns of obese mothers (27.2 vs 48.8 pct, p=0.025). There was no significant difference in inter twin birth weight difference between offspring of gastric bypass (median: 9.9%, IQR: 6.5 to 20.0) vs. obese (median: 14.6%, IQR: 8.2 to 21.6) and BMI matched controls (median: 9.0%, IQR: 6.3 to 12.6, p=0.714). Conclusions: In summary, intrauterine growth delay in twin pregnancies after GB is assumed to be a multifactorial event with altered metabolism as the most important factor. However, special attention must be paid to the particularity of twin pregnancies as they seem to be subject to other additional mechanism.

Glutamate carboxypeptidase II (GCPII) is a metalloprotease implicated in neurological diseases and prostate oncology. While several classes of potent GCPII-specific inhibitors exist, the development of novel active scaffolds with different pharmacological profiles remains a challenge. Virtual screening followed by in vitro testing is an effective means for the discovery of novel active compounds. Structure- and ligand-based pharmacophore models were created based on a dataset of known GCPII-selective ligands. These models were used in a virtual screening of the SPECS compound library (∼209.000 compounds). Fifty top-scoring virtual hits were further experimentally tested for their ability to inhibit GCPII enzymatic activity in vitro. Six hits were found to have moderate to high inhibitory potency with the best virtual hit, a modified xanthene, inhibiting GCPII with an IC50 value of 353 ± 24 nM. The identification of this novel inhibitory scaffold illustrates the applicability of pharmacophore-based modeling for the discovery of GCPII-specific inhibitors.

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