Reversible Morphological Changes Research Articles

Morphological Control of Microtubule-Encapsulating Giant Vesicles by Changing Hydrostatic Pressure.

For the development of artificial cell-like machinery, liposomes encapsulating cytoskeletons have drawn much recent attention. However, there has been no report showing isothermally reversible morphological changes of liposomes containing cytoskeletons. We succeeded in reversibly changing the shape of cell-sized giant vesicles by controlling the polymerization/depolymerization state of cytoskeletal microtubules that were encapsulated in the vesicles using pressure changes. The result indicates that it is possible to manipulate artificial cell models composed of molecules such as lipids and proteins. The findings obtained in this study will be helpful in clarifying the details of cooperation between cytoskeletal dynamics and morphogenesis of biological membranes and in improving the design and construction of further advanced artificial cell-like machinery, such as drug-delivery systems. In addition, the experimental system used in this study can be applied to research to elucidate the adaptive strategy of living organisms to external stimuli and extreme conditions such as osmotic stress and high-pressure environments like the deep sea.

A Solid-State Intrinsically Stretchable Polymer Solar Cell.

An organic solar cell based on a bulk heterojunction of a conjugated polymer and a methanofullerene PC61BM or PC71BM exhibits a complex morphology that controls both its photovoltaic and mechanical compliance (flexibility and stretchability). Here, the donor-acceptor blend of poly(thieno[3,4-b]-thiophene/benzodithiophene) (PTB7) and PC71BM containing a small amount of diiodooctane (DIO) in the spin-casting solution is reported to exhibit elastic deformability. The blend comprises nanometer-size, nanocrystalline grains that are relatively uniformly distributed. Large external deformation is accommodated by relative sliding between the grains. Reorientation of the nanocrystallites and the global reorientation of the PTB7 polymer chain were observed along the stretching direction up to 100% strain, which was reversible as the blend was allowed to relax to 0% strain. The polymer solar cell based on PTB7:PC71BM:DIO with such reversible morphological changes exhibited a rubbery elasticity at room temperature. The device could be stretched up to 100% strain, and the power-conversion efficiency shows a slight increase up to 30% strain and a global increase of power generation as the photoactive area increases with strain. Solar cells were fabricated employing a layer of the PTB7:PC71BM:DIO blend sandwiched between a pair of stretchable transparent electrodes, each comprising a stack of a silver nanowire percolation network and a single-wall carbon nanotube network embedded in the surface of a poly(urethane acylate) elastomer film. The solar cells were semitransparent and could be stretched like a rubbery film by as much as 100% strain. The measured power-conversion efficiency was 3.48%, which was increased to 3.67% after one cycle of stretching to 50% strain and lowered to 2.99% after 100 stretching cycles. The total power generation from the cells was significantly increased, thanks to the expanded active area as the cells were stretched.

Electrochemical activity and morphology of human erythrocytes at optically transparent ITO electrode

The electrochemical activity of a suspension of human erythrocytes was found at potentials above +0.4 V. The limiting current of electrooxidation was found to linearly depend on the cell concentration in the suspension. The electrochemical activity of an erythrocyte suspension is accompanied by reversible changes in the cell morphology only in non-buffered media.

Characterization of nickel catalysts with transient methods

The Ni surface area is a key factor in catalytic performance of supported Ni catalysts employed in heterogeneously catalyzed reactions. For its characterization, transient measurement techniques are powerful but need a proper experimental design and a high level of accuracy. In this study, several transient methods, namely temperature programmed desorption of H2 (H2-TPD), pulsed H2 chemisorption and N2O chemisorption, were applied and evaluated for the characterization of Ni catalysts. Results were compared with those from static H2 chemisorption. Ni powder, as well as NiAlOx and Ni/γ-Al2O3 with varying Ni loadings, synthesized via precipitation and incipient wetness impregnation, respectively, were used as model catalysts. H2-TPD within the temperature range from 84 to 753K is able to completely describe the interaction of H2 with supported Ni. However, a quantitative analysis of the specific Ni surface area based on H2-TPD is difficult whereas pulsed H2 chemisorption leads to comparable results as obtained from static measurements. Adsorption and pre-treatment conditions have a strong impact on the desorption spectra. Reversible morphologic changes of the Ni surface were revealed by H2-TPD when changing the gas atmosphere during pre‐treatment. N2O chemisorption occurs in three steps including fast oxygen uptake, growth of the oxide layer and subsequent layer thickening due to subsurface and bulk oxidation. A separation of surface and subsurface/bulk oxidation of NiAlOx and Ni/γ-Al2O3, both of which are readily oxidized even under mild conditions, is only achievable at temperatures between 190 and 195K. In this temperature range, the ratio of adsorbed oxygen atoms, O, and the number of Ni surface atoms, NiS, (O/NiS) is 0.38±0.07, which can be applied for specific Ni surface area determination. The experimental mode of N2O chemisorption (flow or titration mode) does not influence the extent of subsurface oxidation. The separation of surface and subsurface/bulk oxidation is more feasible in the case of Ni powder. Here, a suitable temperature for Ni surface area determination lies within 265 and 285K with an O/NiS ratio of 0.96±0.05.

15α-methoxypuupehenol Induces Antitumor Effects In Vitro and In Vivo against Human Glioblastoma and Breast Cancer Models.

Studies with 15α-methoxypuupehenol (15α-MP), obtained from the extracts of Hyrtios species, identified putative targets that are associated with its antitumor effects against human glioblastoma and breast cancer. In the human glioblastoma (U251MG) or breast cancer (MDA-MB-231) cells, treatment with 15α-MP repressed pY705Stat3, pErk1/2, pS147CyclinB1, pY507Alk (anaplastic lymphoma kinase), and pY478ezrin levels and induced pS10merlin, without inhibiting pJAK2 (Janus kinase) or pAkt induction. 15α-MP treatment induced loss of viability of breast cancer (MDA-MB-231, MDA-MB-468) and glioblastoma (U251MG) lines and glioblastoma patient-derived xenograft cells (G22) that harbor aberrantly active Stat3, with only moderate or little effect on the human breast cancer, MCF7, colorectal adenocarcinoma Caco-2, normal human lung fibroblast, WI-38, or normal mouse embryonic fibroblast (MEF Stat3fl/fl) lines that do not harbor constitutively active Stat3 or the Stat3-null (Stat3-/-) mouse astrocytes. 15α-MP-treated U251MG cells have severely impaired F-actin organization and altered morphology, including the cells rounding up, and undergo apoptosis, compared with a moderate, reversible morphology change observed for similarly treated mouse astrocytes. Treatment further inhibited U251MG or MDA-MB-231 cell proliferation, anchorage-independent growth, colony formation, and migration in vitro while only moderately or weakly affecting MCF7 cells or normal mouse astrocytes. Oral gavage delivery of 15α-MP inhibited the growth of U251MG subcutaneous tumor xenografts in mice, associated with apoptosis in the treated tumor tissues. Results together suggest that the modulation of Stat3, CyclinB1, Alk, ezrin, merlin, and Erk1/2 functions contributes to the antitumor effects of 15α-MP against glioblastoma and breast cancer progression. Mol Cancer Ther; 16(4); 601-13. ©2017 AACR.

RAFT Polymerization of Dual Responsive Hyperbranched-Star Copolymers of Methacrylic Acid and Poly(Ethylene Glycol)

Smart polymers are materials that respond to external stimuli via reversible morphological changes, making them potential systems for drug delivery applications. In this study, dual-responsive star copolymers with a hyperbranched core composed of ethylene glycol dimethacrylate (EGDMA) - methacrylic acid (MAA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) arms were synthesized via two-step Reversible Addition-fragmentation Chain Transfer (RAFT) block copolymerization. The synthesis involved the formation of the hyperbranched MAA core followed by arm extension with PEGMA. The formation of the hyperbranched core and subsequent copolymerization with PEGMA were verified by FT-IR and 1H-NMR spectroscopic techniques. The distinct EGDMA peak was found at 4.3 ppm while the peak attributed to PEGMA was found at around 3.5 ppm. Furthermore, the synthesized block copolymers were both temperature and pH-responsive with LCST value at 57°C and morphological transition at pH 5.6. The synthesized smart polymer was also biocompatible based on Trypan blue cytotoxicity assay. The inherent dual responsive behavior and biocompatibility of the copolymer render it a good candidate for drug delivery systems.

Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations

Ethnopharmacological relevanceCasearia sylvestris (Salicaceae) is found in South America and presents antiulcerogenic, cytotoxic, antimicrobial, anti-inflammatory and antihypertensive activities. Aim of the studyTo assess the in vivo and ex vivo antitumor action of a fraction with casearins (FC) and its main component - Casearin X-isolated from C. sylvestris leaves. Materials and methodsFirstly, Sarcoma 180 bearing Swiss mice were treated with FC and Cas X for 7 days. Secondly, BALB/c nude animals received hollow fibers with colon carcinoma (HCT-116) or glioblastoma (SF-295) cells and were treated with FC for 4 days. On 5th day, proliferation was determined by MTT assay. ResultsFC 10 and 25mg/kg/day i.p. and 50mg/kg/day oral and Cas X 25mg/kg/day i.p. and 50mg/kg/day oral revealed tumor growth inhibition rates of 35.8, 86.2, 53.7, 90.0 and 65.5% and such tumors demonstrated rare mitoses and coagulation necrosis areas. Similarly, FC reduced multiplying of HCT-116 and SF-295 cells when evaluated by the Hollow Fiber Assay (2.5 and 5mg/kg/day i.p. and 25 and 50mg/kg/day oral), with cell growth inhibition rates ranging from 33.3 to 67.4% (p<0.05). Flow cytometry experiments revealed that FC reduced membrane integrity and induced DNA fragmentation and mitochondrial depolarization (p<0.05). ConclusionsFC and Cas X were efficient antitumor substances against murine and human cancer cells and caused reversible morphological changes in liver, kidneys and spleens, emphasizing clerodane diterpenes as an emerging class of anticancer molecules.

Reversible Morphological Control of Tubulin-Encapsulating Giant Liposomes by Hydrostatic Pressure.

Liposomes encapsulating cytoskeletons have drawn much recent attention to develop an artificial cell-like chemical-machinery; however, as far as we know, there has been no report showing isothermally reversible morphological changes of liposomes containing cytoskeletons because the sets of various regulatory factors, that is, their interacting proteins, are required to control the state of every reaction system of cytoskeletons. Here we focused on hydrostatic pressure to control the polymerization state of microtubules (MTs) within cell-sized giant liposomes (diameters ∼10 μm). MT is the cytoskeleton formed by the polymerization of tubulin, and cytoskeletal systems consisting of MTs are very dynamic and play many important roles in living cells, such as the morphogenesis of nerve cells and formation of the spindle apparatus during mitosis. Using real-time imaging with a high-pressure microscope, we examined the effects of hydrostatic pressure on the morphology of tubulin-encapsulating giant liposomes. At ambient pressure (0.1 MPa), many liposomes formed protrusions due to tubulin polymerization within them. When high pressure (60 MPa) was applied, the protrusions shrank within several tens of seconds. This process was repeatedly inducible (around three times), and after the pressure was released, the protrusions regenerated within several minutes. These deformation rates of the liposomes are close to the velocities of migrating or shape-changing living cells rather than the shortening and elongation rates of the single MTs, which have been previously measured. These results demonstrate that the elongation and shortening of protrusions of giant liposomes is repeatedly controllable by regulating the polymerization state of MTs within them by applying and releasing hydrostatic pressure.

Reversible morphological changes of assembled supramolecular amphiphiles triggered by pH-modulated host-guest interactions.

Reversible template-directed micellar-size and shape modulation by virtue of host-guest reversible docking of molecular templates at the micellar-solvent interface was achieved in water. By combining a π-electron deficient bipyridinium-based gemini amphiphile which is capable of binding and aligning with a π-electron rich tri(ethylene glycol)-disubstituted 1,5-diaminonaphthalene, a switchable detergent system which operates through the pH-responsive formation of bisammonium dications was realised. The binding of the 1,5-diaminonaphthalene guest to the bipyridinium-based micellar aggregate superstructure can be actuated by the addition of acid and base. Upon the addition of acid, protonation of the guest forming the dication deactivates molecular recognition with the charged head groups of the micellar aggregate by Coulombic repulsion. This process is completely reversible upon the addition of base, whereby the guest reintercalates into the superstructure -again forming donor-acceptor π-π stacks at the micellar-solvent interface amongst contiguous surfactant head groups. Synchrotron small angle X-ray scattering and dynamic laser light scattering confirm that this form of reversible directionally-templated micellisation results in an oblate spheroid-to-lamellar micelle morphological transition with a stabilising net decrease in the free energy of micellisation of 1.4 kcal mol(-1) per hydrophobic tail.

Indirect Nanoplasmonic Sensing to Probe with a High Sensitivity the Interaction of Water Vapor with Soot Aerosols

We demonstrate in this work that the indirect nanoplasmonic sensing lets us follow the adsorption/desorption of water molecules on soot particles that are a major contributor of the global warming. Increasing the relative humidity of the surrounding medium we measure a shift in wavelength of the localized surface plasmon resonance response of gold nanodisks on which soot particles are deposited. We show a singular and reversible blue shift with hydrophilic aircraft soot particles interpreted from a basic model as a reversible morphological change of the soot aggregates. This new method is highly sensitive and interesting to follow the change of optical properties of aerosols during their aging in the atmosphere, where they can adsorb and react with different gas molecules.

Photoinduced macroscopic morphological transformation of an amphiphilic diarylethene assembly: reversible dynamic motion.

Self-assembled microstructures of an amphiphilic diarylethene featuring an alkyl chain and triethylene glycol groups showed a photoinduced reversible morphological change in water. Reversible photoisomerization of the core diarylethene gave rise to a reversible morphological transformation between colorless microspheres and colored fibers. When colorless microspheres were irradiated with UV light, colored fibers were formed, and when the colored fibers were irradiated with visible light, the spheres were restored to their original positions where the spheres originally existed. This system showed reversible morphological change through not only photoirradiation but also temperature change. These behaviors can be interpreted as a phase transition between the sphere and fiber states. The dynamic process of the phase transition was monitored by polarized optical microscopy (POM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). It was revealed that the formation of fibers upon UV irradiation occurred radially at the surface of the sphere and the formation of the spheres upon visible-light irradiation occurred at the middle of the fiber. The unique photoinduced mechanical motion provides useful information for the design of sophisticated photoactuators.

A generic microfluidic biosensor of G protein-coupled receptor activation – impedance measurements of reversible morphological changes of reverse transfected HEK293 cells on microelectrodes

Flowcell with micro-IDEs (250–500 μm) covered with both stable and reverse transfected cells overexpressing membrane receptors to demonstrate impedance responses to serial injections of analyte.

Functional evaluation using multifocal electroretinogram after selective retina therapy with a microsecond-pulsed laser.

To evaluate the changes of retinal function with multifocal electroretinogram (mfERG), and estimate the association between functional and structural changes after selective retina therapy (SRT) with microsecond-pulsed laser in comparison to continuous wave laser photocoagulation (cwPC). Selective retina therapy and cwPC were applied with 10 × 10 shots and 1/2 lesion-width on the retina in the right and left eyes of 20 healthy Chinchilla Bastard rabbits, respectively. Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), and mfERG were performed before, and on days 1, 7, and 30 after both laser treatments. The mean ratios of amplitudes and implicit times of N1 and P1 from eight hexagons covering laser-treated retinal lesions/total retina were measured. Histology was obtained after killing three rabbits at each time period to observe the anatomic changes after both laser treatments. The mean ratios of amplitudes of N1 and P1 in SRT lesions did not change significantly for 30 days after laser treatment. Only subtle reductions of the mean ratios of N1 and P1 amplitudes on day 1, thereafter the amplitudes showed the trend to recover toward baseline values. Histology and OCT revealed temporary and reversible morphologic changes after SRT, which restored to normal within 1 month. However, the mean ratios of N1 amplitudes on days 7 and 30 (P = 0.010, P < 0.001, respectively), and P1 amplitudes on days 7 and 30 (P < 0.001, P < 0.001, respectively) declined significantly in cwPC lesions compared with baseline. Disorganization and atrophic changes were identified on histology and OCT after cwPC. The results suggest that SRT preserved retinal function as well as anatomical structure after treatment.

The angiopoietin-Tie2 signaling axis in the vascular leakage of systemic inflammation

The ability of small blood vessels to undergo rapid, reversible morphological changes is essential for the adaptive response to tissue injury or local infection. A canonical feature of this response is transient hyperpermeability. However, when leakiness is profound or persistent, adverse consequences accrue to the host, including organ dysfunction and shock. A growing body of literature identifies the Tie2 receptor, a transmembrane tyrosine kinase highly enriched in the endothelium, as an important regulator of vascular barrier function in health and in disease. The principal ligands of Tie2, Angiopoietins 1 and 2, exert opposite effects on this receptor in the context of inflammation. This review will focus on recent studies that have illuminated novel aspects of the exquisitely controlled Tie2 signaling axis while proposing unanswered questions and future directions for this field of study.

Monte Carlo simulation of temperature-induced reversible morphological changes between sphere and vesicle formed by AB diblock copolymers

Temperature-induced reversible morphological changes of micelles formed by AB diblock copolymers in a selective solvent for A blocks was studied through Monte Carlo simulation. When only hydrophobic B blocks are temperature-sensitive, the micelle morphology changes from sphere at high temperature to vesicle with a decrease in temperature. When the system was heated back to high temperature, the vesicles transform into spheres, indicating reversible morphological changes with temperature. However, the simulation results show that the pathways of morphological changes between sphere and vesicle depend on temperature change rate. The pathway of the sphere changing into vesicle under a quenching process is different from the pathway of the vesicle changing into sphere when the system was directly heated to the higher temperature. Moreover, the time consumed in the simulation for vesicle transformation into sphere upon heating is significantly shorter than that for the reverse process upon quenching. By contrast, when changing the temperature gradually, the pathways of morphological transitions from sphere to vesicle and from vesicle to sphere are almost identical. Moreover, the time consumed in the simulation for the annealing and gradual heating processes are nearly the same. This pathway differences observed when directly and gradually changing the temperature of the system are further elucidated by investigating the contact number variation between B blocks and solvents with simulation time. On the other hand, when the hydrophilic blocks and hydrophobic blocks are both temperature-sensitive, the introduction of the temperature-sensitivity of hydrophilic blocks hinders the morphological transition from sphere to vesicle under annealing conditions, and only larger spheres can be obtained after the annealing process when the degree of temperature-sensitivity of blocks A is rather high. Meanwhile, the simulation results show that the morphological transitions are still reversible under a slow temperature change rate when the hydrophilic blocks and hydrophobic blocks are both temperature-sensitive.

Evaluation of Acute Post-Shock Wave Lithotripsy Renal Changes by Dynamic Magnetic Resonance Imaging: A Prospective Clinical Study

We studied acute renal morphological and hemodynamic changes aftershock wave lithotripsy of renal stones. A total of 60 adult patients with a single renal stone 25mm or less in a radiologically normal urinary tract were eligible for shock wave lithotripsy and included in analysis. Study exclusion criteria were hypertension, diabetes mellitus, previous recent stone management and other contraindications to shock wave lithotripsy. Renal perfusion and morphological changes were evaluated by dynamic magnetic resonance imaging before, and 2to4 hours and 1 week after lithotripsy. In all cases there was a statistically significant decrease in renal perfusion 1 week after shock wave lithotripsy compared to before and 2 to 4hours after lithotripsy (66% vs 71% and 72% of the aortic blood flow, respectively, p<0.05). At 1-week followup 39 unobstructed renal units (65%) showed no significant difference in renal perfusion at any time while 21 (35%) obstructed renal units showed a significant decrease in renal perfusion compared to before and 2 to 4 hours after lithotripsy (63% vs 76% and 75%, p = 0.003 and 0.005, respectively). Hematomas were observed in 7 cases (12%) 2 to 4 hours after lithotripsy, of which 5 were subcapsular and 2 were intrarenal. Three subcapsular hematomas resolved after 1 week. Localized loss of corticomedullary differentiation was observed in 2 patients (3.3%) with intrarenal hematoma 2 to 4hours after treatment. Generalized loss of corticomedullary differentiation wasobserved 1 week after lithotripsy in 5 cases (8.3%). Shock wave lithotripsy alone induces minimal, reversible acute renal morphological changes and does not induce significant changes in renal perfusion. Posttreatment obstruction has a major effect on renal perfusion on thetreated side and must be managed urgently.

Insights into embryo defenses of the invasive apple snail Pomacea canaliculata: egg mass ingestion affects rat intestine morphology and growth.

BackgroundThe spread of the invasive snail Pomacea canaliculata is expanding the rat lungworm disease beyond its native range. Their toxic eggs have virtually no predators and unusual defenses including a neurotoxic lectin and a proteinase inhibitor, presumably advertised by a warning coloration. We explored the effect of egg perivitellin fluid (PVF) ingestion on the rat small intestine morphology and physiology.Methodology/Principal FindingsThrough a combination of biochemical, histochemical, histopathological, scanning electron microscopy, cell culture and feeding experiments, we analyzed intestinal morphology, growth rate, hemaglutinating activity, cytotoxicity and cell proliferation after oral administration of PVF to rats. PVF adversely affects small intestine metabolism and morphology and consequently the standard growth rate, presumably by lectin-like proteins, as suggested by PVF hemaglutinating activity and its cytotoxic effect on Caco-2 cell culture. Short-term effects of ingested PVF were studied in growing rats. PVF-supplemented diet induced the appearance of shorter and wider villi as well as fused villi. This was associated with changes in glycoconjugate expression, increased cell proliferation at crypt base, and hypertrophic mucosal growth. This resulted in a decreased absorptive surface after 3 days of treatment and a diminished rat growth rate that reverted to normal after the fourth day of treatment. Longer exposure to PVF induced a time-dependent lengthening of the small intestine while switching to a control diet restored intestine length and morphology after 4 days.Conclusions/SignificanceIngestion of PVF rapidly limits the ability of potential predators to absorb nutrients by inducing large, reversible changes in intestinal morphology and growth rate. The occurrence of toxins that affect intestinal morphology and absorption is a strategy against predation not recognized among animals before. Remarkably, this defense is rather similar to the toxic effect of plant antipredator strategies. This defense mechanism may explain the near absence of predators of apple snail eggs.

Lack of protracted behavioral abnormalities following intermittent or continuous chronic mild hypoxia in perinatal C57BL/6 mice

Several prospective studies indicated perinatal hypoxia as risk factor for psychiatric disorders like schizophrenia. It is thought that hypoxia prior to or during birth may contribute to alterations leading to the protracted clinical manifestation during young adulthood. However, only a small fraction of children with a history of perinatal hypoxia develop later psychotic symptoms, therefore it is not known if hypoxia alone is sufficient to trigger long-term behavioral changes. Here we exposed C57BL/6 mice from postnatal day 3–7 (P3–P7) to two established paradigms of chronic mild hypoxia (10% ambient O2), intermittent and continuous. Subsequently, mice were analysed during young adult stages using several basic behavioral tests. Previous studies demonstrated severe, but only transient, cortical damage in these paradigms; it is not clear, if these reversible morphological changes are accompanied by long-term behavioral effects. We found that neither intermittent nor continuous perinatal hypoxia induced long-term behavioral alterations. This may be due to the high regenerative capacity of the perinatal brain. Other possibilities include a potential resistance to perinatal hypoxia of the mouse strain used here or a level of hypoxia that was insufficient to trigger significant behavioral changes. Therefore, our data do not exclude a role of perinatal hypoxia as risk factor for psychiatric disorders. They rather suggest that either other, more severe hypoxic conditions like anoxia, or the presence of additional factors (as genetic risk factors) are necessary for generating long-term behavioral abnormalities.

Reversible alterations in cardiac morphology and functions in a patient with Cushing's syndrome.

SummaryA 45-year-old female was referred for endocrine evaluation of an incidental mass (31×24 mm in diameter) on the right adrenal gland. The patient was normotensive and nondiabetic, and had no history of generalised obesity (body weight, 46 kg at 20 years of age and 51.2 kg on admission); however, her waist-to-hip ratio was 0.97. Elevated urinary free cortisol levels (112–118 μg/day) and other findings indicated adrenocorticotrophic hormone-independent Cushing's syndrome due to right adrenocortical adenoma. Echocardiography before adrenalectomy revealed concentric left ventricular (LV) hypertrophy with a particular increase in interventricular septum thickness leading to impaired systolic and diastolic functions. Upon surgical remission of hypercortisolism, the asymmetric hypertrophy disappeared and the cardiac dysfunctions were considerably ameliorated. Although the mechanism(s) by which excessive cortisol contributes to LV wall thickness remain(s) unclear, serial echocardiography and cardiac multidetector-row computed tomography may support the notion that abnormal fat deposition in the myocardium owing to hypercortisolism appears to be an important factor for the reversible change in the cardiac morphology.Learning points Patients with Cushing's syndrome occasionally exhibit severe LV hypertrophy related to systolic and diastolic dysfunctions although they have neither hypertension nor diabetes mellitus.Biological remission of hypercortisolism can normalise structural and functional cardiac parameters and help in differentiating the cardiac alterations induced by excessive cortisol from those induced by other diseases.Excessive lipid accumulation within the heart before myocardial fibrosis may be implicated in reversible alterations in the cardiac morphology by Cushing's syndrome.Early diagnosis and treatment of Cushing's syndrome appear to be pivotal in preventing irreversible cardiac dysfunctions subsequent to cardiovascular events and heart failure.

Low Toxicity β-Cyclodextrin-Caged 4,4′-Bipyridinium-bis(siloxane): Synthesis and Evaluation

The toxicity of viologens can be significantly reduced by including them in tight [2]rotaxane structures alongside β-cyclodextrin, thus turning them into candidates of pharmaceutical interest. Here, we report a synthesis pathway for a benign viologen, by capping a small β-cyclodextrin-caged molecule, the 4,4'-bipyridine, with minimal-length presynthesized axle-stopper segments of the propyl-3-pentamethyldisiloxane type. After 90 min from the oral administration to laboratory mice, the product concentration in the bloodstream reaches a value equivalent to 0.634% of the initial dose of 800 mg·kg(-1). As compared to the nude viologen having the same structure, which proved to be lethal in doses of 40 mg·kg(-1), the product induces reversible morphological changes in the liver, kidney, lung, and cerebellum, up to a dose of 400 mg·kg(-1), with higher dosages giving rise to a chronic slow evolution.