Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague-Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p < 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8-mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days, and procured at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, i.e. the percentage wound area changes, did not show an increase with NPY (p = 0.938) but did with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism is elusive but likely involves NPY receptor subtypes other than Y2R.
Pain is a severe and debilitating complication of metastatic bone cancer. Current analgesics do not provide sufficient pain relief for all patients, creating a great need for new treatment options. The Src kinase, a non-receptor protein tyrosine kinase, is implicated in processes involved in cancer-induced bone pain, including cancer growth, osteoclastic bone degradation and nociceptive signalling. Here we investigate the role of dasatinib, an oral Src kinase family and Bcr-Abl tyrosine kinase inhibitor, in an animal model of cancer-induced bone pain. Daily administration of dasatinib (15 mg/kg, p.o.) from day 7 after inoculation of MRMT-1 mammary carcinoma cells significantly attenuated movement-evoked and non-evoked pain behaviour in cancer-bearing rats. Radiographic - and microcomputed tomographic analyses showed significantly higher relative bone density and considerably preserved bone micro-architecture in the dasatinib treated groups, suggesting a bone-preserving effect. This was supported by a significant reduction of serum TRACP 5b levels in cancer-bearing rats treated with 15 mg/kg dasatinib. Furthermore, immunoblotting of lumbar spinal segments showed an increased activation of Src but not the NMDA receptor subunit 2B. These findings support a role of dasatinib as a disease modifying drug in pain pathologies characterized by increased osteoclast activity, such as bone metastases.
Objective To identify risk factors for and outcomes after SARS-CoV-2 infection and severe COVID-19 in pregnancy Design Prospective population-based cohort study Setting Denmark Population All pregnancies between 1 March and 31 October 2020 Methods Using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records, we compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Severe infection was defined as hospital admission due to COVID-19. Main Outcome Measures Pregnancy, delivery, maternal, and neonatal outcomes. Results Among 82,682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (OR 2.19 [1.41–3.41]) and being foreign born (OR 2.12 [1.70–2.64]). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74 [1.00–7.51]), smoking (OR 4.69 [1.58–13.90]), infection after gestational age in weeks (GA) 22 (GA 22–27: OR 3.77 [1.16–12.29]; GA 28–36: OR 4.76 [1.60–14.12]) and having asthma (OR 4.53 [1.39–14.79]). We found no difference in any obstetric or neonatal outcomes. Conclusions Severe outcomes of SARS-CoV-2 infection in pregnancy are rare. Funding The Danish Ministry of Higher Education and Science (Reg. 0237-00007B) and The Region of Southern Denmark and Region Zealand’s shared fund for joint health research projects (Reg. A767) Keywords Severe acute respiratory syndrome coronavirus 2; COVID-19; Obstetric delivery; Pregnancy complications; Pregnancy outcome; Cohort studies; Prospective studies.
Introduction Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. The majority of cases are asymptomatic and in cases with complications, the diagnosis may be a challenge and the surgical approach is not obvious. The primary aim of the present study was to evaluate the diagnostic process and surgical approach in relation to clinical presentation. The secondary aim was to evaluate the severity of postoperative complications. Methods A two-center, retrospective analysis of all children below the age of 15 years, operated for complications to MD during the period from January 2003 to December 2016. Results A total of 58 patients were included. In the 40 patients presenting with an acute abdomen an average of 2.3 preoperative diagnostic investigations was performed. In only five cases an MD was recognized preoperatively. In the 18 patients presenting with rectal bleeding or melaena an average of 3.2 preoperative investigations were performed and in only one case the MD was recognized preoperatively. Laparoscopy was the surgical approach in 36 patients (62%) with a conversion in 8. Postoperative complications were seen in two patients (Clavien-Dindo II and IIIb). Conclusion Despite extensive diagnostic work-out an MD was recognized in only a few patients preoperatively. Laparoscopy was the surgical approach in two-thirds of the patients.
Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p < 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8 mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days and collected at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, specifically the percentage changes in wound area, did not show an increase with NPY (p = 0.907), but there was an increase with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (used as a positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism remains elusive but likely involves NPY receptor subtypes other than Y2R.
