Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this technology focus on the generation of featured microparticles for improving the function of the systems. Here, we present a new type of microparticles with gelatin methacrylate (GelMa) cores and poly(L-lactide-co-glycolide) (PLGA) shells for synergistic and sustained drug delivery applications. The microparticles were fabricated by using GelMa aqueous solution and PLGA oil solution as the raw materials of the microfluidic double emulsion templates, in which hydrophilic and hydrophobic actives, such as doxorubicin hydrochloride (DOX, hydrophilic) and camptothecine (CPT, hydrophobic), could be loaded respectively. As the inner cores were polymerized in the microfluidics when the double emulsions were formed, the hydrophilic actives could be trapped in the cores with high efficiency, and the rupture or fusion of the cores could be avoided during the solidification of the microparticle shells with other actives. The size and component of the microparticles can be easily and precisely adjusted by manipulating the flow solutions during the microfluidic emulsification. Because of the solid structure of the resultant microparticles, the encapsulated actives were released from the delivery systems only with the degradation of the biopolymer layers, and thus the burst release of the actives was avoided. These features of the microparticles make them ideal for drug delivery applications.

Objectives: The anti-inflammatory effects of O-1602 and cannabidiol (CBD), the ligands of G proteinYcoupled receptor 55 (GPR55), on experimental acute pancreatitis (AP) were investigated.Methods: Acute pancreatitis was induced in C57BL mice by intraperitoneal injection of 50 Kg/kg cerulein hourly, with a total of 6 times. Drugs (O-1602, 10 mg/kg, or CBD, 0.5 mg/kg) were given by intraperitoneal injection 2 times at 30 minutes before the first injection and immediately before the fifth cerulein injection. At 3 hours after the last injection, the blood, the lungs, and the pancreas were harvested for the pancreatic enzyme activity, myeloperoxidase activity, and pro-inflammatory cytokines measurement; and the expressions of GPR55 mRNA and protein in the pancreas were detected.Results: Cannabidiol or O-1602 treatment significantly improved the pathological changes of mice with AP and decreased the enzyme activities, IL-6 and tumor necrosis factor > levels, and the myeloperoxidase activities in plasma and in the organ tissues. G proteinYcoupled receptor 55 mRNA and protein expressed in the pancreatic tissue, and the expressions were decreased in the mice with AP, and either CBD or O-1602 attenuated these changes to a certain extent.Conclusion: Cannabidiol and O-1602 showed anti-inflammatory effects in mice with AP and improved the expression of GPR55 in the pancreatic tissue as well.

Laparoscopy combined with transvaginal management appeared to result in less bleeding, shorter operative times, and a lower rate of complication in patients with uterine wound rupture and dense adhesions.

Hypertension is a serious health problem particularly for African-Americans. Previous studies have suggested that angiotensinogen (AGT) gene locus is involved in human essential hypertension. We have recently shown that an A/G polymorphism at -217 in the promoter of the AGT gene is associated with essential hypertension especially in African-Americans. We report here that A/G polymorphism at -217 affects the glucocorticoid-induced promoter activity of the human AGT gene. We show that recombinant glucocorticoid receptor (GR) binds strongly to the AGT gene promoter when nucleoside A is present at -217, and dexamethasone treatment increases the interleukin 6 induced promoter activity of reporter constructs containing nucleoside A at -217. Similarly cotransfection of GR and C/EBP beta or C/EBP delta increases the promoter activity of reporter construct containing nucleoside A at -217. Since AGT is an acute phase protein, we propose that increased expression of -217A allele of the AGT gene by glucocorticoids and C/EBP family of transcription factors may be involved in essential hypertension.

Angiotensinogen (AGT) is the precursor of one of the most important vasoactive hormone angiotensin II and this gene locus is associated with human essential hypertension. AGT is an acute phase protein and its gene expression is regulated by IL-6. Previous studies have identified three potential STAT-3 binding sites (APREs) located between −160 and −280 of the hAGT gene promoter but only APRE-1 (located between −271 and −279) was shown to be a bonafide enhancer for IL-6-induced promoter activity. We show here that APRE-2, located between −236 and −247, is indeed an HNF-1α-binding site and plays an important role in basal and IL-6 induced promoter activity of this gene. Our chromatin immunoprecipitation (ChIP) assay shows that HNF-1α binds to this region of the hAGT gene promoter and its recruitment is increased in the presence of IL-6 in Hep3B cells. We also show that the promoter activity of a deletion construct containing only 223 bp of the hAGT gene promoter (that contains only APRE-3) is increased after IL-6 treatment. Our ChIP assay shows that IL-6 treatment recruits STAT-3 to APRE-3 and suggests that this is also an IL6 responsive element. We have previously shown that GR binds to the proximal promoter of the hAGT gene. Since GR physically interacts with STAT-3, we propose that transcription factors GR, STAT-3, and HNF-1α that bind to the nucleotide sequence located between −160 and −280 of the hAGT gene promoter are responsible for IL-6 induced promoter activity of this gene.

Aims Pulmonary arterial hypertension is a severe complication in patients with congenital heart disease and poses a significant risk to women wishing to become pregnant. This study describes the clinical presentation, maternal outcomes and risk factors for the peripartum period in women with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD). Methods All pregnant women with PAH-CHD who were admitted for delivery in a tertiary center between February 2011–September 2016 were included. Logistic regression analysis was used to identify predictors of the combined endpoint of maternal death, severe heart failure requiring treatment, or pulmonary hypertensive crisis. Results Ninety-three women (94 pregnancies) were included. Average age was 27.5 ± 4.4 years. Thirty (31.9%) patients had Eisenmenger syndrome, 51 (54.3%) had pulmonary arterial hypertension associated with systemic-to-pulmonary shunts, and 13 (13.8%) had pulmonary arterial hypertension with corrected congenital heart disease. Twenty-three (24.5%) women required admission for delivery within two days from presentation. Elective Cesarean section was performed in 95.7% of women, with intravertebral anesthesia in 93.6%. Fifty-one (54.2%) patients received pulmonary arterial hypertension therapies during pregnancy. Six (6.4%) women died, 33 (35.1%) developed heart failure and 10 (10.6%) had a pulmonary hypertensive crisis. Patients who met the combined endpoint ( n = 34, 36.2%) were more likely to have Eisenmenger syndrome or repaired defects ( p < 0.001). Other risk factors in the multivariate model included lower arterial blood oxygen saturation, higher brain natriuretic peptide, and pericardial effusion on echocardiography. Conclusion Maternal mortality and morbidity remain high in PAH-CHD patients, who should be counseled on the risks of pregnancy and managed in a tertiary multidisciplinary environment to improve prognosis.

No abstract

No abstract