Peripartum cardiomyopathy: A review.

Peripartum cardiomyopathy is a rare type of heart failure manifesting towards the end of pregnancy or in the months following delivery, in the absence of any other cause of heart failure. There is a wide range of incidence across countries reflecting different population demographics, uncertainty over definitions and under-reporting. Race, ethnicity, multiparity and advanced maternal age are considered important risk factors for the disease. Its etiopathogenesis is incompletely understood and is likely multifactorial, including hemodynamic stresses of pregnancy, vasculo-hormonal factors, inflammation, immunology and genetics. Affected women present with heart failure secondary to reduced left ventricular systolic function (LVEF <45%) and often with associated phenotypes such as LV dilatation, biatrial dilatation, reduced systolic function, impaired diastolic function, and increased pulmonary pressure. Electrocardiography, echocardiography, magnetic resonance imaging, endomyocardial biopsy, and certain blood biomarkers aid in diagnosis and management. Treatment for peripartum cardiomyopathy depends on the stage of pregnancy or postpartum, disease severity and whether the woman is breastfeeding. It includes standard pharmacological therapies for heart failure, within the safety restrictions for pregnancy and lactation. Targeted therapies such as bromocriptine have shown promise in early, small studies, with large definitive trials currently underway. Failure of medical interventions may require mechanical support and transplantation in severe cases. Peripartum cardiomyopathy carries a high mortality rate of up to 10% and a high risk of relapse in subsequent pregnancies, but over half of women present normalization of LV function within a year of diagnosis.

Reported Signs, Symptoms, and Diagnostic Tests Before Cardiotoxicity Among Women With Breast Cancer: A Pilot Study.

BACKGROUND: Cardiotoxicity after cancer treatment is a potentially preventable life-threatening complication among women with breast cancer. There is no algorithm to identify women with breast cancer at risk of cardiotoxicity. OBJECTIVES: We quantified signs and symptoms as well as selected laboratory values among women with breast cancer who developed cardiotoxicity. METHODS: The clinical characteristics (n = 15) were collected from electronic health records. Spearman correlation coefficients and a nonparametric statistical test were used to analyze data. RESULTS: Significant statistical differences were detected in the laboratory values comparing the first and second half of 6 months before cardiotoxicity including alanine aminotransferase (U/L) (30.67 ± 26.27 and 42.31 ± 35.65, respectively; P = .03, Cohen's d = 0.37). A negative correlation was found between estimated glomerular filtration rate and new onset of more than 1 sign or symptom (Spearman's ρ = -0.5, P = .06). CONCLUSIONS: Investigating clinical characteristics before cardiotoxicity may determine the mechanism(s) and identify high-risk patients.

Thermo- and photoinduced spin state switching in an iron(II) 2D coordination network associated with large light-induced thermal hysteresis and tuning of dimensionality via ligand modulation.

Three iron(ii) complexes, [Fe(L1)2(NCS)2(MeOH)2] (1), [Fe(L1)2(NCSe)2(MeOH)2] (2), and [Fe(L2)2(NCS)2]n (3) (L1 = 2,5-dipyridyl-3,4-ethylenedioxythiophene and L2 = 2,5-diethynylpyridinyl-3,4-ethylenedioxythiophene), have been synthesized using redox-active luminescent ethylenedioxythiophene (EDOT)-based ligands, and characterized by variable temperature single-crystal X-ray diffraction, (photo)magnetic, optical reflectivity, and spectroscopy studies. Magneto-structural investigations revealed that 1 and 2 are mononuclear with a FeN4O2 octahedral coordination geometry and remain in a high-spin (HS) (S = 2) state in a temperature range of 2-280 K. Interestingly, a 2D coordination network structure with FeN6 surrounding each iron center was observed for 3, which exhibits reversible thermo-induced spin-state switching between the paramagnetic high-spin (HS) (S = 2) and diamagnetic low-spin (LS) (S = 0) states at around 105 K (T1/2). Furthermore, optical reflectivity and photomagnetic measurements at low temperature confirmed that 3 shows reversible ON/OFF switching between the photoinduced excited paramagnetic HS metastable state and diamagnetic LS state under light irradiation (ON mode using red light and OFF mode using green light). Finally, the photoinduced excited HS state can be reversibly relaxed back to the diamagnetic ground LS state by heating the system at ca. 88 K (TLIESST = 88 K) (light-induced excited spin state trapping (LIESST) effect). Furthermore, 3 also showed an exciting and unique 18 K wide light-induced thermal hysteresis (LITH) effect above liquid nitrogen temperature (100 K). DFT and CASSCF level theoretical calculations were utilized to better understand the magneto-structural correlations of these complexes.

Molecular insights of cigarette smoke condensate-activated NLRP3 inflammasome in THP-1 cells in a stage-specific atherogenesis.

BACKGROUND: Smoking induces excessive inflammation which is associated with all the stages of atherosclerosis. Earlier, we reported Nod-like receptor protein 3 (NLRP3) inflammasome activation as a pro-atherosclerotic property of cigarette smoking. In the present study, we aimed to explore the underlying detailed upstream mechanism and the cellular status of putative downstream molecules of cigarette smoke condensate (CSC)-activated NLRP3 inflammasome in atherosclerotic disease. METHODS AND RESULTS: THP-1 monocytes, macrophages and foam cells represent crucial stages of atherogenesis as initiation, progression and development. To determine the upstream molecular regulators of smoking-induced NLRP3 inflammasome in atherogenesis, Myeloid differentiation primary response 88/Nuclear Factor kappa-light-chain-enhancer of activated B cells (MyD88/NF-κB) and Suppressor of cytokine signaling 3/Signal transduction and activator of transcription 3 (SOCS3/STAT3) pathways were elucidated. Stage-specific THP-1 cells were treated with MyD88 and SOCS3/STAT3 inhibitors. The results showed that MyD88 inhibition markedly attenuated the expression of NLRP3 markers (NLRP3, caspase-1, Interleukin (IL)-1ß and IL-18), IL-6, SOCS3 and NF-κB. Moreover, the secretory levels of pro-cytokines were also significantly reduced in culture media. In contrast, no changes were observed with SOCS3/STAT3 inhibitor. Further, ac-vyad-cmk, an inflammasome inhibitor was used to explore the downstream targets of CSC-activated NLRP3 inflammasome in atherosclerotic process. The transcriptional profiling of 25 atherosclerotic markers was carried out using ExProfile™ Custom Gene qPCR Arrays. CSC exposure upregulated the expression of 17 genes and downregulated 4 genes in a stage-specific manner. Inhibitory experiments showed aberrant changes in CSC-regulated genes. Altogether, 15 molecules were common in all three stages. CONCLUSION: The findings may suggest that MyD88/NF-κB pathway is an upstream regulator of NLRP3 inflammasome underlying smoking-induced atherosclerosis. Notably, 15 atherosclerotic molecules associated with endothelial dysfunction, scavenger receptors, cholesterol esterification and matrix-metalloproteins were found downstream to CSC-activated NLRP3 inflammasome.

ON/OFF Photoswitching and Thermoinduced Spin Crossover with Cooperative Luminescence in a 2D Iron(II) Coordination Polymer.

A 2D coordination polymer, {[Fe(L)2(NCSe)2]·6MeOH·14H2O}n (1; L = 2,5-dipyridylethynylene-3,4-ethylenedioxythiophene), has been synthesized based on a redox active luminescence ligand. 1 possesses a 2D [4 × 4] square-grid network where the iron(II) center is in a FeN6 octahedral coordination environment. 1 displays reversible thermoinduced high-spin (HS; S = 2) to diamagnetic low-spin (LS; S = 0) ON/OFF spin-state switching with a T1/2 value of 150 K. Interestingly, optical reflectivity and photomagnetic studies at 10 K under light irradiation revealed an efficient conversion to a photoinduced metastable HS excited state from a LS ground state. Remarkably, the photoexcited HS state can be reversibly switched ON and OFF by using 625 and 850 nm light-emitting-diode lights. Intriguingly, the thermal dependence of the luminescence intensity of the maximum emission at 524 nm for 1 shows a minimum at around the spin-crossover (SCO) temperature, indicating a cooperative nature between the SCO and luminescence properties. Theoretical calculations confirmed the above findings.

Activation of NLRP3 inflammasome assembly is associated with smoking status of patients with coronary artery disease.

OBJECTIVE: Cigarette smoke is considered as a sterile inflammatory stimulus which triggers an innate immune response, accountable for vascular events. Previously, we reported smoking-induced NLRP3 inflammasome activation in the pathogenesis of atherosclerosis through caspase-1 activation and secretion of pro-cytokines (interleukin (IL)-1ß and IL-18) in vitro and in vivo. Therefore, the present study aimed to reconnoitre the association of cigarette smoking and NLRP3 inflammasome activation ex vivo in human subjects with coronary atherosclerosis. METHODS AND RESULTS: In order to establish and validate the association between smoking status and NLRP3 inflammasome ex vivo, mononuclear cells were isolated from smokers with angiographically-proven coronary artery disease (CAD); non-smokers with CAD; smokers without CAD, and healthy non-smokers (controls) (n = 20 each). The transcriptional and translational expression of NLRP3 inflammasome markers i.e. NLRP3, pro-caspase-1, caspase-1, pro-IL-1ß, IL-1ß, pro-IL-18 and IL-18 was significantly increased (2 to 7-fold) in smokers with CAD vs non-smokers with CAD; and smokers without CAD vs non-smoker controls. In addition, the oxidative stress, an upstream mediator of NLRP3 inflammasome was evaluated and found to be significantly augmented in smokers vs non-smokers (with and without CAD respectively). Further, the levels of serum cotinine, oxidative stress markers (8-isoprostane and 8-oxo-2́'-deoxyguanosine), caspase-1 and pro-cytokines (IL-1ß and IL-18) were also higher in smokers vs non-smokers. Moreover, the levels of pro-cytokines were positively correlated with caspase-1 and serum cotinine, corroborating the secretion of cytokines in a caspase-1-dependent manner. CONCLUSION: Our data may imply NLRP3 inflammasome as a mediator of the pro-atherosclerotic property of cigarette smoking in atherosclerotic patients.

Exposure of cigarette smoke condensate activates NLRP3 inflammasome in vitro and in vivo: A connotation of innate immunity and atherosclerosis.

OBJECTIVE: Smoking is known to have detrimental effects on cardiovascular system. However, the potential molecular basis of smoking-induced atherosclerosis remains unclear. NLRP3 inflammasome is implicated in perpetuation of inflammatory response in atherosclerosis. Therefore, we aimed to explore the cytotoxic effects of cigarette smoke condensate (CSC) on the activation of NLRP3 inflammasome in vitro and in vivo. METHODS: For in vitro study, the pro-atherogenic effects of CSC were evaluated in THP-1 monocytes with different dose concentrations (0.1, 1, 5, 10 and 20 µg/ml) for varied time periods (6, 12, 24 and 48 h). For in vivo study, 30 male C57BL/6J mice were employed. 6 mice were sacrificed for baseline investigations. 24 mice were randomly divided into four groups: Group-I:Control mice, Group-II:CSC model, Group-III:High-fat diet(HFD) model, and Group-IV:HFD + CSC model for 14 weeks (n = 6/group). The group-II and IV mice were injected with 720 µg CSC/20 g body weight intraperitoneally (6 days/week). RESULTS: In vitro, higher dosage of CSC (20 µg/ml) was toxic to cells as significant decline in cell viability and proliferation was observed. Furthermore, the mRNA expression of NLRP3 inflammasome and its pro-cytokine levels were significantly augmented on CSC exposure in a dose-dependent manner but impeded in time-dependent manner. In vivo, CSC and HFD independently augmented the expression of NLRP3 inflammasome (~4-10 fold-change) along with pro-cytokine levels in Group-II and III vs Group-I mice whereas, HFD + CSC treatment demonstrated synergistic effects in Group-IV. CONCLUSION: Our data suggest that CSC activates NLRP3 inflammasome in vitro and in vivo and collectively with HFD has synergistic effects in vivo that may promote atherosclerosis.

Aberrant ETS-1 signalling impedes the expression of cell adhesion molecules and matrix metalloproteinases in non-segmental vitiligo.

Cell adhesion is a complex process that involves multiple molecules on the cell surface (ie cell adhesion molecules [CAMs]), surrounding cells and extracellular matrix (ECM). Repigmentation in vitiligo is dependent on the ECM remodelling and cellular migration, primarily attributed to the transcriptional activation of matrix metalloproteinases (MMPs). In this study, we aimed to demonstrate the role of ETS-1 signalling in the regulation of MMPs and CAMs. Therefore, we studied the expression of ETS-1, MMPs (MMP-2, MMP-9) and CAMs including E-cadherin, ITGA-1 and ICAM-1 in vitiligo (both active and stable) ex vivo. Further, we compared melanocyte morphology and their adhesion towards collagen IV and laminin between control and vitiligo groups in vitro. Also, we silenced ETS-1 in melanocytes cultured from control skin and observed post-silencing effect on above-mentioned MMPs and CAMs. We perceived absent ETS-1 and significantly reduced CAMs and MMPs in vitiligo compared with normal skin. Scanning electron microscopy (SEM) revealed a translucent material surrounding individual melanocytes in stable vitiligo and controls, whereas active vitiligo melanocytes demonstrated loss of this extracellular substance. Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS-1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absent ETS-1 expression in both stable and active non-segmental vitiligo seems to impede the expression of CAMs, apart from MMPs, probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease.

Exposure of cigarette smoke condensate activates NLRP3 inflammasome in THP-1 cells in a stage-specific manner: An underlying role of innate immunity in atherosclerosis.

BACKGROUND: Smoking is known to affect all the phases of atherosclerosis, thus is considered as an independent and major risk factor. The underlying mechanism responsible for the atherogenic effects of smoking is still uncertain and a major concern. Recent evidence implicates NLRP3 inflammasome, an innate immunity component in the pathogenesis of atherosclerosis. Therefore, we hypothesized that NLRP3 inflammasome may be an associated pathway between smoking and atherosclerosis. METHODS AND RESULTS: Differentiation in monocytes, macrophages and foam cells are the key stages in atherosclerotic plaque development, best mimicked by THP-1 cells. Therefore, to determine whether cigarette smoke condensate (CSC) could induce differentiation of THP-1 monocytes into macrophages, morphological changes and the expression levels of the inflammatory surface markers, i.e. CD11b, CD14 and CD36 were analyzed. The results showed that CD14 and CD36 levels were significantly increased in CSC-treated THP-1 monocytes. Further, we investigated the effect of CSC exposure on the status of NLRP3 inflammasome markers, i.e. NLRP3, pro-caspase-1, caspase-1, pro-IL-18, pro-IL-1ß, IL-1ß and IL-18 in a stage-specific manner. For this, THP-1 monocytes, PMA-differentiated macrophages and oxidized-low density lipoprotein (ox-LDL)-induced macrophage foam cells were exposed to 10 µg/ml of CSC for 6 h. CSC exposure significantly upregulated the expression of NLRP3 inflammasome in CSC-treated cells at both transcriptional and translational levels. Moreover, downstream pro-cytokines, i.e. IL-1ß and IL-18 levels were also significantly increased in culture supernatants of CSC-exposed cells. CONCLUSION: These observations suggest that CSC exposure may activate NLRP3 inflammasome in a stage-specific manner and may promote initiation and progression of atherosclerosis.

Peripheral Cemento-Ossifying Fibroma withUncommon Clinical Presentation: A Case Report / Fibroma periférico cemento-ossificante con una presentación clínica poco común: Reporte de caso

Abstract Peripheral cemento-ossifying fibroma (PCOF) is a reactive gingival over growth, occurring frequently in the maxillary anterior region of teenage and young females. Peripheral cemento-ossifying fibroma (PCOF) is supposed to be originating from periosteum and/or periodontal ligament. A large number of factors have been implicated in the pathogenesis of PCOF, which includes trauma, local irritation, calculus and hormonal disturbances. The definitive diagnosis of PCOF is based upon its clinical, radiological and histological features. Because of the high recurrence rate (8-20%) of PCOF, a close post-operative follow-up is required. Herewith, we are presenting a case of PCOF in 24-year old female patient at an uncommon location.

Resumen El fibroma cemento-osificante periférico (PCOF, por sus siglas en inglés) es un crecimiento gingival reactivo, que se produce con frecuencia en la región anterior del maxilar en adolescentes y mujeres jóvenes. Se supone que el fibroma cemento-osificante periférico (PCOF) se origina en el periostio y/o el ligamento periodontal. Una gran cantidad de factores han sido implicados en la patogénesis de PCOF, dentro de las que se incluye trauma, irritación local, cálculo y alteraciones hormonales. El diagnóstico definitivo de PCOF se basa en sus características clínicas, radiológicas e histológicas. Debido a la alta tasa de recurrencia (8-20%) , se requiere un seguimiento post-operatorio estricto. Mediante este artículo presentamos un caso de PCOF en una paciente de 24 años de edad y el manejo teraupético.