3,6,9,12,15,18,21,24-Octaoxaheptacos-26-yn-1-ol - CAS 1351556-81-4

Noninvasively monitoring activated fibroblasts is of great value for understanding the dynamic process of myocardial fibrosis after myocardial infarction (MI). This study aimed to evaluate the feasibility of 68Ga-labeled fibroblast activation protein inhibitor 04 (68Ga-FAPI-04) for monitoring reparative fibrosis and reactive fibrosis after MI. MI models were prepared by ligation of the left anterior descending (LAD) coronary artery and validated by electrocardiogram and 18F-FDG PET/CT 1 day after MI and hematoxylin and eosin (HE) staining. 68Ga-FAPI-04 PET/CT scans (1, 3, 6, 9, 12, 15, 18, 21, 28, and 35 days after MI) were carried out in MI rats and sham-operated rats without ligation of LAD. Blocking experiments were carried out on MI rats on day 7 after MI with 68Ga-FAPI-04 and excessive FAPI-04. Autoradiography, HE staining, Masson's trichrome staining, and immunofluorescence staining were carried out for ex vivo validation. The infarcted area with decreased or defective myocardial metabolic activity in 18F-FDG PET/CT correspondingly showed high 68Ga-FAPI-04 uptake in the MI rats. The myocardial tracer uptake was significantly different between MI and sham-operated rats from day 1 to 28 after MI and reached peak value 6 days after MI (0.806 ± 0.257%ID/cc vs 0.199 ± 0.012%ID/cc, P < 0.05). Tracer uptake at the infarcted myocardium and normal tissues in MI rats decreased significantly after blocking. Obvious tracer uptake was confirmed by autoradiography, and immunofluorescence staining showed FAP+ cells in the infarcted myocardium and border zone. Masson's trichrome staining of the heart sections of MI rats at different times suggested the presence of myocardial fibrosis. 68Ga-FAPI-04 uptake was not observed in the distal uninjured myocardium throughout the observation period. In conclusion, 68Ga-FAPI-04 PET could noninvasively monitor the activated fibroblasts in the early stage post acute MI and may be helpful for evaluating the degree of reparative fibrosis, while reactive fibrosis monitoring still needs further study.

Introduction:Primary congenital glaucoma (PCG) is a challenging disease that needs to be surgically managed with more innovative methods. Conventional incisional surgery, such as goniotomy and trabeculotomy, has a primary high success rate, but does not seem to be a very effective treatment in advanced stages.Design:A prospective clinical case study.Purpose:To qualify the outcome, in terms of success rate, of goniotomy combined with trabeculotomy as a surgical option to treat eyes affected by PCG with a corneal diameter larger than 14 mm.Patients and methods:This study included 50 eyes of 50 patients diagnosed with PCG with corneal diameter larger than 14 mm who underwent ab interno goniotomy combined with ab externo trabeculotomy. Intraocular pressure (IOP) was measured preoperatively and 24 months postoperatively. A statistical analysis was performed to detect correlations between the success rate and corneal diameter, preoperative IOP, age of onset, axial length, and consanguinity. The main outcome was reduction in IOP; secondary outcomes were factors affecting the success rate, complications, and the need for additional surgical intervention to control IOP. Results:The mean age of the patients was 18.86±9.94 months. Males made up 52% of cases and females 48% of cases. Positive consanguinity was present in 38% of cases. Axial length ranged between 20 and 22 mm, with a mean of 20.98±0.8 mm. Mean preoperative IOP was 29.56±3.36 mmHg, which decreased postoperatively to 12.6±2.5, 14.1±3.2, 16.8±5.5, 14.4±2.3, 14.3±1.6, 14.3±1.6, 14.3±1.6, 14.3±1.7, and 14.3±1.7 mmHg at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months respectively (p˂0.001). Use of medical treatment was decreased from 2.7±0.4 preoperatively to 1.4±0.7 postoperatively (p˂0.001). Hyphema was the only complication that appeared, occurring in 47% of cases. The success rate was 94%. Complete success (IOP 21 mmHg with treatment). The success rate was significantly related to preoperative IOP, corneal diameter, axial length, consanguinity, and age of onset (p˂0.001). All cases were followed for 24 months.Conclusion:Ab interno goniotomy combined with ab externo trabeculotomy improves the success rate of buphthalmos surgery. A significant correlation was detected between success rate and preoperative IOP, corneal diameter, axial length, consanguinity, and age of onset.

The sow at parturition is challenged with respect to energy status due to increases in energetic expenses associated with 1) nest building 2) uterine contractions, and 3) colostrum production. A previous study indicated that sows were depleted of glucogenic energy around farrowing. The aim was to investigate whether intravenous infusion of glucose from observed nest-building behavior to 24 h postpartum affected the farrowing kinetics and colostrum production in sows. Ten multiparous sows (DanBred landrace × DanBred Yorkshire) were fitted with a jugular vein catheter on each side (one for infusion and the other one for blood sampling). Sows were infused with either 0.9% saline (CON; n = 5) or 10% glucose (GLU; n = 5) solution at a constant rate of 125 mL/h. From day 108 of gestation, sows were fed once daily with 3.33 kg of a standard lactation diet. During farrowing, sows were monitored to register the onset of farrowing, time of birth, birth status (live or dead), sex, stillbirth rate (SR), and weight of newborn piglets. Farrowing assistance (FA) was provided when the birth interval exceeded 60 min. In late gestation, 1 mL of blood was collected every third hour for blood gas analysis and every sixth hour for harvesting plasma. During farrowing, 1 mL (for blood gas) and 9 mL of blood were collected at 0, 3, 6, 9, 12, 15, 18, 21, and 24 h in milk (HIM). Colostrum and milk samples were collected at 0, 6, 12, 18, 24, and 36 HIM and also at 3, 10, 17, and 24 d in milk. Compared with CON sows, GLU infusion decreased the SR (16.1% vs. 7.4%; P = 0.03), FA (21% vs. 9.0%; P = 0.01), and surprisingly also blood glucose at the onset of farrowing (5.53 vs. 5.09 mmol/L; P = 0.03), respectively. A tendency to higher plasma lactate at the onset of farrowing (P = 0.05) but decreased piglet mortality from 0 to 24 h (P = 0.06) was also found for GLU sows. No effects of treatment on farrowing duration or mean birth intervals were found. Lactate in whole blood (P = 0.003) and plasma (P = 0.002) was increased for GLU sows as compared with CON sows during the colostrum period. No effect of GLU infusion was seen on colostrum and milk composition and yield. The increase in lactate was most likely due to a shift toward a greater proportion of glucose oxidation and insufficient O2 supply to fuel uterine contractions. In conclusion, infusion of glucose reduced the frequency of SR and FA, and improved energy status of the sow which seems to be crucial to enhance total piglet survival.