Eplerenone in the Treatment of Polypoidal Choroidal Vasculopathy

Overactivation of mineralocorticoid receptor pathways has been implicated in the pathophysiology of central serous chorioretinopathy (CSCR). Recently, mineralocorticoid receptor antagonists such as eplerenone have demonstrated success in treating subretinal fluid in CSCR. This case demonstrates a patient who was initially presumed to have subretinal fluid secondary to CSCR and was started on a trial of oral eplerenone. It quickly became evident that her subretinal fluid was secondary to a peripapillary polypoidal choroidal vasculopathy network, but she demonstrated a significant improvement with oral eplerenone. To the authors'' knowledge, this is the first case of eplerenone use to treat polypoidal choroidal vasculopathy.Key Words: Eplerenone, Mineralocorticoid antagonist, Polypoidal choroidal vasculopathy     

Association of Interleukin-1β-31C/T, -511T/C and -3954C/T Single Nucleotide Polymorphism and Their Blood Plasma Level in Acquired Aplastic Anemia

Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1β) gene polymorphisms, (IL-1β-31, IL-1β-511 and IL-1β-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR–RFLP) method and IL-1β plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1β was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1β-3954 genotype. IL-1β-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1β gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1β gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.     

Potent antifibrillatory effects of intrapericardial nitroglycerin in the ischemic porcine heart

OBJECTIVES: We investigated the antiarrhythmic effects of intrapericardial nitroglycerin (NTG) during acute myocardial ischemia in the porcine heart. BACKGROUND: Nitroglycerin is a nitric oxide donor that exerts potent effects on the cardiovascular system. Intrapericardial administration allows investigation of pharmacologic actions on cardiac tissue in an in vivo system while minimizing the confounding influences of systemic effects. METHODS: In 29 closed-chest pigs, myocardial ischemia was induced by intraluminal balloon occlusion of the left anterior descending coronary artery. Arrhythmia incidence was monitored during 5-min balloon inflations performed without drug and at 15, 45, 75, and 105 min after NTG (4,000 microg bolus) administered by percutaneous transatrial access into the pericardial space. Electrocardiograms were monitored for ischemia-induced T-wave alternans (TWA), a marker of electrical instability. The antiadrenergic potential of NTG was investigated by examining the drug's suppression of dobutamine-induced increase in myocardial contractility. RESULTS: Control coronary artery occlusion provoked ventricular fibrillation (VF) in all animals. Intrapericardial NTG suppressed VF at 45 min in all six pigs (p < 0.05) and reduced TWA across a parallel time course (from 459.1 +/- 144.4 microV before drug to 42.22 +/- 13.96 microV at 45 min, p = 0.047). The antifibrillatory effect occurred as early as 15 min and persisted for up to 75 min. Augmentation of maximum of the first time derivative of left ventricular pressure by dobutamine was blunted by intrapericardial NTG (from 3,999 +/- 196 mm Hg/s before NTG to 3,543 +/- 220 mm Hg/s at 15 min, p = 0.012). CONCLUSIONS: Intrapericardial NTG exerts a robust antifibrillatory action. Potential mechanisms include reduction in electrical instability and blunting of adrenergic effects.     

Revisiting rhino-orbito-cerebral acute invasive fungal sinusitis in the era of COVID-19: pictorial review

Emergency Radiology - COVID-19 patients have been found to have an increased incidence of superadded fungal infections because of multiple factors such as impaired cell-mediated immunity,...     

Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases

Background and aimsPreconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility.Materials and methodsThis was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant.ResultsMedian and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15–42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression.ConclusionSimultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.     

“Ride-on” technique and other simple and logical solutions to counter most common complications of silicone implants in augmentation rhinoplasty

Augmentation rhinoplasty can be carried out using a wide range of materials including autologous bone and/or cartilage as well as alloplasts. Use of biologic bone and cartilage grafts results in lower infection rates, but they are associated with long-term resorption and donor-site morbidity. Alloplastic materials, in particular silicone, have been associated in literature with extrusion, necrosis of the tip, mobility and deviation or displacement of the implant, immobile nasal tip and infection. However, they have the advantages of being readily available and easy to reshape with no requirement for harvesting autografts.

Aim:

To overcome these problems associated with silicone implants for which the authors have devised a novel technique, the “rideon technique”.

Materials and Methods:

The present study was carried out on 11 patients over a period of 4 years. The authors have devised a simple technique to fix the silicone implant and retain it in place. Restricting the implant to only dorsum avoided common complications related to the silicone implant.

Results:

The authors have used this technique in 11 patients with encouraging results. Follow-up ranged from 12 months to 36 months during which patients were assessed for implant mobility, implant extrusion and tip necrosis. There was no incidence of above mentioned complications in these patients.

Conclusion:

The “rideon technique” provides excellent stability to silicone implants and restricting the implant only to dorsum not only eliminates chances of tip necrosis and thus implant extrusion but also maintains natural shape, feel and mobility of the tip.KEY WORDS: Alloplasts, autografts, rhinoplasty, silicone implants     

Usefulness of persistent symptoms of depression to predict physical health status 12 months after an acute coronary syndrome

Previous research has focused on the relation between depression after an acute coronary syndrome (ACS) and subsequent cardiac morbidity and mortality. However, the relation between depression and quality of life during recovery remains unclear. We investigated whether symptoms of depression during hospitalization for ACS or the course of depressive symptoms after ACS predict physical health status 12 months after ACS, controlling for physical health status at the time of the ACS. This was a prospective study of 425 patients with ACS assessed with the Beck Depression Inventory (BDI) and Short Form 12 (SF-12) Health Survey during hospitalization and 12 months later. Linear regression was used to assess the relation between in-hospital BDI scores and BDI symptom trajectory after ACS with physical health status 12 months later, controlling for baseline physical health status, age, gender, Killip class, history of acute myocardial infarction, and cardiac diagnosis. Baseline BDI scores predicted 12-month physical health (p <0.001). Compared with nondepressed patients, only patients with persistent symptoms of depression were at risk for poorer physical health. Patients with newly developed depressive symptoms after ACS were at slightly increased risk for worsened physical health (p = 0.060), whereas patients with transient depressive symptoms were not at increased risk. In conclusion, these results underscore the importance of assessing depression at the time of ACS and on an ongoing basis.     

Multiscale model of light harvesting by photosystem II in plants

The first step of photosynthesis in plants is the absorption of sunlight by pigments in the antenna complexes of photosystem II (PSII), followed by transfer of the nascent excitation energy to the reaction centers, where long-term storage as chemical energy is initiated. Quantum mechanical mechanisms must be invoked to explain the transport of excitation within individual antenna. However, it is unclear how these mechanisms influence transfer across assemblies of antenna and thus the photochemical yield at reaction centers in the functional thylakoid membrane. Here, we model light harvesting at the several-hundred-nanometer scale of the PSII membrane, while preserving the dominant quantum effects previously observed in individual complexes. We show that excitation moves diffusively through the antenna with a diffusion length of 50 nm until it reaches a reaction center, where charge separation serves as an energetic trap. The diffusion length is a single parameter that incorporates the enhancing effect of excited state delocalization on individual rates of energy transfer as well as the complex kinetics that arise due to energy transfer and loss by decay to the ground state. The diffusion length determines PSII’s high quantum efficiency in ideal conditions, as well as how it is altered by the membrane morphology and the closure of reaction centers. We anticipate that the model will be useful in resolving the nonphotochemical quenching mechanisms that PSII employs in conditions of high light stress.The first step of photosynthesis is light harvesting, the absorption and conversion of sunlight into chemical energy. In photosynthetic organisms, the functional units of light harvesting are self-assembled arrays of pigment–protein complexes called photosystems. Antenna complexes absorb and transfer the nascent excitation energy to reaction centers, where long-term storage as chemical energy is initiated (1). In plants, photosystem II (PSII) flexibly responds to changes in sunlight intensity on a seconds to minutes time scale. In dim light, under ideal conditions, PSII harvests light with a >80% quantum efficiency (2), whereas, in intense sunlight PSII dissipates excess absorbed light safely as heat via nonphotochemical quenching pathways (3). The ability of PSII to switch between efficient and dissipative states is important for optimal plant fitness in natural sunlight conditions (4). Understanding how PSII’s function arises from the structure of its constituent pigment−protein complexes is a prerequisite for systematically engineering the light-harvesting apparatus in crops (5–7) and could be useful for designing artificial materials with the same flexible properties (8, 9).Recent advances have established structure−function relationships within individual pigment−protein complexes, but not how these relationships affect the functioning of the dynamic PSII (grana) membrane (10). Electron microscopy and fitting of atomic resolution structures (11) place the pigment−protein complexes in the grana membrane in close proximity, enabling long-range transport. Indeed, connectivity of excitation between different PSII reaction centers has been discussed since 1964 (12), suggesting that the functional unit for PSII must involve a large area of the membrane. Two limiting cases have been used to model PSII light harvesting: The lake model assumes perfect connectivity between reaction centers across the membrane; alternatively, the membrane can be described as a collection of disconnected “puddles” of pigments that each contain one reaction center (1, 13). At present, however, resolving the spatiotemporal dynamics within the grana membrane on the relevant length (tens to hundreds of nanometers) and time (1 ps to 1 ns) scales experimentally is not possible. Structure-based modeling of the grana membrane, however, can access this wide range of length and time scales.The dense packing of the major light-harvesting antenna (LHCII, discs), which is a trimeric complex, and PSII supercomplexes (PSII-S, pills) in the grana membrane is shown in Fig. 1 A and B. PSII-S is a multiprotein complex (14) that contains the PSII core reaction center dimer, along with several minor light-harvesting complexes and LHCII (Fig. 1A, Inset). Electronic excited states in LHCII and PSII-S are delocalized over several pigments (15–17), making conventional Förster theory inadequate to describe the excitation dynamics. On the protein length scale, generalized Förster (18, 19) calculations between domains of tightly coupled chlorophylls agree very well with more exact methods [e.g., the zeroth-order functional expansion of the quantum-state diffusion model (ZOFE) approximation to non-Markovian quantum state diffusion (20)] for simulating the excitation population dynamics (21, 22). This agreement suggests that the primary quantum phenomenon involved in PSII energy transfer is the site basis coherence that arises from excited states delocalized across a few (approximately three to four) pigments.Open in a separate windowFig. 1.Accurate simulation of chlorophyll fluorescence dynamics from thylakoid membranes using structure-based modeling of energy transfer in PSII. (A and B) The representative mixed (A) and segregated (B) membrane morphologies generated using Monte Carlo simulations and used throughout this work. PSII-S are indicated by the light teal pills, and LHCII, which are trimeric complexes, are indicated by the light grey-green circles. The segregated membrane forms PSII-S arrays and LHCII pools. As shown schematically in A (Bottom) existing crystal structures of PSII-S (14) and LHCII (24) were overlaid on these membrane patches to establish the locations of all chlorophyll pigments. The light teal and light grey-green dashed lines outline the excluded area associated with PSII-S and LHCII trimers respectively, in the Monte Carlo simulations. The chlorophyll pigments are indicated in green, and the protein is depicted by the grey cartoon ribbon. PSII-S is a twofold symmetric dimer of pigment−protein complexes that are outlined by black lines. LHCII-S (strongly bound LHCII), CP26, CP29, CP43, and CP47 are antenna proteins, and RC indicates the reaction center. The inhomogeneously averaged rates of energy transfer between strongly coupled clusters of pigments were calculated using generalized Förster theory. (C) Simulated fluorescence decay of the mixed membrane (solid black line) and the PSII component of experimental fluorescence decay data from thylakoid membranes from ref. 26 (red, dotted line). Inset shows the lifetime components and amplitudes of the simulated decay as calculated using our model with a Gaussian convolution (σ = 20 ps) (black line) or by fitting to three exponential decays (green bars).Here, we construct a generalized Förster model for the ∼10⁴ pigments covering the few-hundred-nanometer length scale of the grana membrane that correctly incorporates the dynamics occurring within and between complexes on the picosecond time scale. We show how delocalized excited states, or excitons, in individual complexes affect light harvesting on the membrane length scale. The formation of excitons is sufficient to explain the high quantum efficiency of PSII in dim light. The model, by being an accurate representation of the complex kinetic network that underlies PSII light harvesting, provides mechanistic explanations for long-observed biological phenomena and sets the stage for developing a better understanding of PSII light harvesting in high light conditions.