Regenerative medicine therapy: adipose derived extracellular vesicles in viral myocarditis

Objective: Myocarditis, inflammation of the heart muscle, is an autoimmune heart disease that can be caused by viruses, bacteria and toxins. Myocarditis can lead to dilated cardiomyopathy (DCM) and heart failure. Currently there are no disease-specific therapies for treating myocarditis or preventing progression to DCM. Adipose Extracellular Vesicles (AEVs) are lipid bilayer nanoparticles that are released into the outside environment of adipocytes and provide promising regenerative potential for inflammatory diseases like myocarditis. Methods: Lipoaspirate was obtained from women and men and AEVs isolated from the lipoaspirate using tangential flow filtration. We injected wild type male BALB/c mice with 250uL AEVs (1×10^10 EV/mL) intraperitoneally or sucrose control on day -1, 0, 1 with viral infection on day 0. Mice were harvested on day 10 post infection at the peak of myocarditis. Results: We found that male mice treated with AEVs from a female patient had a significantly higher body weight (p=0.0003), less calcification in the gut (p=0.001) and less myocardial inflammation (p=0.007) than controls. Mouse hearts analyzed by qRT-PCR revealed that AEV treated mice had significantly lower relative gene expression of cell markers for total immune cells (CD45, p=0.002), macrophages (CD11b, p=0.002, F4/80, p=0.0004); specifically M2 macrophages (Chi313, p=0.003), as well as CD3+ (p=0.007) and CD4+ T cells (p=0.01) than controls. Additionally, we found that mice treated with AEVs from a male patient also had significantly less myocardial inflammation (p=0.01). Conclusion: AEVs could provide an innovative therapy to reduce cardiac inflammation and decrease the risk of developing DCM following myocarditis

Sex and age differences in sST2 in cardiovascular disease

AimsThe goal of this study was to determine whether sex and age differences exist for soluble ST2 (sST2) for several cardiovascular diseases (CVDs).MethodsWe examined sST2 levels using an ELISA kit for myocarditis (n = 303), cardiomyopathy (n = 293), coronary artery disease (CAD) (n = 239), myocardial infarct (MI) (n = 159), and congestive heart failure (CHF) (n = 286) and compared them to controls that did not have CVDs (n = 234).ResultsMyocarditis occurred in this study in relatively young patients around age 40 while the other CVDs occurred more often in older individuals around age 60. We observed a sex difference in sST2 by age only in myocarditis patients (men aged 38, women 46, p = 0.0002), but not for other CVDs. Sera sST2 levels were significantly elevated compared to age-matched controls for all CVDs: myocarditis (p ≤ 0.0001), cardiomyopathy (p = 0.0009), CAD (p = 0.03), MI (p = 0.034), and CHF (p < 0.0001) driven by elevated sST2 levels in females for all CVDs except myocarditis, which was elevated in both females (p = 0.002) and males (p ≤ 0.0001). Sex differences in sST2 levels were found for myocarditis and cardiomyopathy but no other CVDs and were higher in males (myocarditis p = 0.0035; cardiomyopathy p = 0.0047). sST2 levels were higher in women with myocarditis over 50 years of age compared to men (p = 0.0004) or women under 50 years of age (p = 0.015). In cardiomyopathy and MI patients, men over 50 had significantly higher levels of sST2 than women (p = 0.012 and p = 0.043, respectively) but sex and age differences were not detected in other CVDs. However, women with cardiomyopathy that experienced early menopause had higher sST2 levels than those who underwent menopause at a natural age range (p = 0.02).ConclusionWe found that sex and age differences in sera sST2 exist for myocarditis, cardiomyopathy, and MI, but were not observed in other CVDs including CAD and CHF. These initial findings in patients with self-reported CVDs indicate that more research is needed into sex and age differences in sST2 levels in individual CVDs

Efficacy of mometasone furoate nasal spray in the treatment of acute rhinosinusitis

Abstract Background Acute rhinosinusitis (ARS) refers to a group of disorders characterized by inflammation of the respiratory epithelium of the nose and paranasal sinuses lasting from 7 to 28 days. In the treatment of ARS in addition to an antibiotic, intranasal corticosteroids hasten the clearance of bacteria, decrease the frequency and severity of disease recurrence, and reduce the duration of infection. The purpose is to compare the efficacy of the combination of mometasone furoate nasal spray (MFNS) with amoxicillin and amoxicillin alone in the treatment of acute rhinosinusitis. A total of 120 patients (≥ 12 years) were randomized into 2 groups: group A (N: 60) receiving amoxicillin 500 mg thrice daily alone and group B (N: 60) receiving amoxicillin 500 mg thrice daily and MFNS 200 μg twice daily for 7 days. Patients were followed up after 7 days. The Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire was taken before and after. The total score of SNOT-22 was compared between the groups. Results There was a reduction in the mean total SNOT score in both groups from 21.32 ± 11.29 to 9.37 ± 6.55 in group A and from 26.68 ± 11.97 to 3.07 ± 3.46 in group B which were statistically significant (p < 0.001) in both groups. The posttreatment mean score with the amoxicillin group was 9.31 ± 6.55 and that of the amoxicillin and mometasone furoate group was 3.07 ± 3.46, and their mean difference was 6.3 ± 0.95. In comparison, MFNS with amoxicillin was significantly (p < 0.001) superior than amoxicillin alone. Conclusion Patients receiving amoxicillin alone or amoxillin with MFNS, both  showed improvement of symptoms in ARS. However, amoxicillin with MFNS showed significantly higher improvement and relief of symptoms in ARS than amoxicillin alone