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Abstract

The main objective of this study was to evaluate the intensity and character of the inflammatory reaction caused by an innovative polyester-polyurethane vascular prosthesis implanted into the abdominal aorta of 9 Beagle dogs aged 1-3 years. At 6 and 12 months post implantation the prostheses were removed and tissues samples were examined using 2 methods: histology and immunohistochemistry (IHC). Histology slides stained with hematoxylin and eosin (H&E) were evaluated for the intensity of inflammation by observing the density of inflammatory cells and graded 1 to 4 (1- light inflammation, 4 – severe inflammation). The pro-inflammatory mediator tumor necrosis factor-alpha (TNFα) and two anti-inflammatory mediators, interleukin 1 receptor antagonist (IL1ra), and interleukin 10 (IL10), were also assessed in the tissue samples by IHC methods. Mean (n=5) inflammation grade in H&E slides at 6 months post-implantation (6Mpost) was 2 and mean (n=4) inflammation grade at 12 months (12Mpost) was almost 3. IHC staining showed that TNFα and IL1ra in tissue samples obtained from 6Mpost dogs were expressed at the same intensity indicating equal pro- and anti-inflammatory cytokine levels. However, in the 12Mpost tissues TNFα was expressed more intensely than IL1ra and IL10. Moreover, in 2 dogs at 12Mpost, there were signs of infection assessed on the basis of neutrophil infiltration in the prostheses. In conclusion, the assessment of pro-inflammatory mediators such as TNFα and anti-inflammatory mediators, such as IL1ra and IL10, can help to interpret the intensity of the inflammatory process directed at synthetic prostheses.
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Abstract

B a c k g r o u n d: A novel paradigm of diastolic heart failure with preserved ejection fraction (HFpEF) proposed the induction of coronary microvascular dysfunction by HFpEF comorbidities via a systemic pro-infl ammatory state and associated oxidative stress. Th e consequent nitric oxide deficiency would increase diastolic tension and favor fi brosis of adjacent myocardium, which implies not only left ventricular (LV), but all-chamber myocardial stiff ening. Our aim was to assess relations between low-grade chronic systemic infl ammation and left atrial (LA) pressure-volume relations in real-world HFpEF patients. Me t h o d s: We retrospectively analyzed medical records of 60 clinically stable HpEFF patients in sinus rhythm with assayed high-sensitive C-reactive protein (CRP) during the index hospitalization. Subjects with CRP >10 mg/L or coexistent diseases, including coronary artery disease, were excluded. LV and LA diameters and mitral E/E’ ratio (an index of LA pressure) were extracted from routine echocardiographic 46 Cyrus M. Sani, Elahn P.L. Pogue, et al. records. A surrogate measure of LA stiff ness was computed as the averaged mitral E/e’ ratio divided by LA diameter. R e s u l t s: With ascending CRP tertiles, we observed trends for elevated mitral E/e’ ratio (p <0.001), increased relative LV wall thickness (p = 0.01) and higher NYHA functional class (p = 0.02). Th e LA stiffness estimate and log-transformed CRP levels (log-CRP) were interrelated (r = 0.38, p = 0.003). On multivariate analysis, the LA stiff ness index was independently associated with log-CRP (β ± SEM: 0.21 ± 0.07, p = 0.007) and age (β ± SEM: 0.16 ± 0.07, p = 0.03), which was maintained upon adjustment for LV mass index and relative LV wall thickness. C o n c l u s i o n s: Low-grade chronic infl ammation may contribute to LA stiff ening additively to age and regardless of the magnitude of associated LV hypertrophy and concentricity. LA stiff ening can exacerbate symptoms of congestion in HFpEF jointly with LV remodeling.
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Abstract

The prevalence of vitamin D deficiency in the American and European population is estimated to be extremely high. Although fewer people today suff er from serious health problems related to calcium and phosphate metabolism resulting from vitamin D deficiency, there are more and more studies suggesting that calcitriol may play an important role in the pathogenesis of other diseases in virtually every body system. A growing body of research shows that through its ubiquitously expressed receptor, calcitriol displays potent anti-angiogenic an anti-inflammatory activity. Th is review summarizes recent discoveries regarding these non-classical eff ects of vitamin D and their clinical implications. Data collection focused on the prevention and treatment of ocular diseases as well as on the underlying mechanisms.
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