An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Background. While metformin is the first-line pharmacological treatment of diabetes mellitus type 2, this drug is not considered safe to use in pregnant women because of its unknown consequences for the fetus. In this study, we aimed to investigate the biodistribution of metformin in the pregnant chinchilla, a species exhibiting placental characteristics comparable with the pregnant woman. Furthermore, we aimed to investigate the expression of metformin transporters in humans and chinchillas, respectively, in order to evaluate the pregnant chinchilla as a novel animal model for the use of metformin in pregnancy. Methods. Three chinchillas in the last part of gestation were injected with [11C]-metformin and scanned by PET/CT for 70 minutes to visualize the distribution. To investigate the difference in expression of placenta transporters between humans and chinchillas, PCR was performed on samples from five chinchilla placentae and seven human placentae. Results. Dynamic PET with [11C]-metformin showed that the metformin distribution in chinchillas was similar to that in nonpregnant humans, with signal from kidneys, liver, bladder, and submandibular glands. Conversely, no radioactive signal was observed from the fetuses, and no metformin was accumulated in the chinchilla fetus when measuring the SUV. PCR of placental mRNA showed that the human placentae expressed OCT3, whereas the chinchilla placentae expressed OCT1. Conclusion. Since metformin did not pass the placenta barrier in the pregnant chinchilla, as it is known to do in humans, we do not suggest the chinchilla as a future animal model of metformin in pregnancies.

BackgroundGestational diabetes occurs in 3–4% of all pregnancies, thereby being one of the leading pregnancy diseases in developed countries. The disease poses important health implications for both mother and child. Several animal models exist in this field, but with significant limitations. Consequently we want to introduce the pregnant chinchilla as a novel animal model of gestational diabetes. The chinchilla is excelled for various reasons; it gives birth to one or two cubs, is pregnant for 115 day and has a histological similar placenta barrier as compared with the human one. Since the chinchilla has never been used in diabetic studies, we aimed to show that it is possible to make it diabetic, before making a gestational model.Streptozotocin is by far the most applied method to induce diabetes in animal models, mimicking the ethology of diabetes type 1. However, since gestational diabetes is due to insulin resistance, we wanted to use high fructose feed as a method to induce diabetes.MethodsTwelve chinchillas were included in the study, six of which received high fructose diet to induce diabetes and six who received control diets. Blood glucose was monitored using Abbott Libre Freestyle glucometer. After 19 weeks the animals were euthanized and organs and blood withdrawn for analysis.Preliminary resultsNon‐fasting plasma glucose levels in chinchillas fed with high fructose diet was 19.3 ± 6.9 mmol/l, compared to controls 11.1 ± 2.2 mmol/l, p=0.056. Furthermore, DXA scans showed significant higher body fat percentage among fructose animals, p=0.043 compared to controls. HBA1C was, however, not affected in any of the groups.ConclusionWe have proven it possible to induce high blood glucose levels in the chinchilla by using high fructose diet. Because of the low sample size the blood glucose levels were, however, not statistically significant between groups. In spite of this, we consider the chinchilla a promising option for a future model of gestational diabetes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.