The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons

Rational design of a (S)-selective-transaminase for asymmetric synthesis of (1S)-1-(1,1′-biphenyl-2-yl)ethanamine

Amine transaminases offer an environmentally sustainable synthesis route for the production of pure chiral amines. However, their catalytic efficiency toward bulky ketone substrates is greatly limited by steric hindrance and therefore presents a great challenge for industrial synthetic applications. We hereby report an example of rational transaminase enzyme design to help alleviate these challenges. Starting from the Vibrio fluvialis amine transaminase that has no detectable catalytic activity toward the bulky aromatic ketone 2-acetylbiphenyl, we employed a rational design strategy combining in silico and in vitro studies to engineer the transaminase enzyme with a minimal number of mutations, achieving an high catalytic activity and high enantioselectivity. We found that, by introducing two mutations W57G/R415A, detectable enzyme activity was achieved. The rationally designed variant, W57F/R88H/V153S/K163F/I259M/R415A/V422A, showed an improvement in reaction rate by more than 1716-fold toward the bulky ketone under study, producing the corresponding enantiomeric pure (S)-amine (enantiomeric excess (ee) value of >99%)

Development and application of novel engineered transaminase panels assisted by in- silico rational design for the production of chiral amines

There is a high demand for the synthesis of chiral amines as building blocks for a large number of industrially valuable compounds. Transaminases (TAm) offer an enzymatic route for the synthesis of chiral amines that avoids complex chemical synthesis [1]. However, their catalytic efficiency towards bulky ketone substrates is greatly limited by steric hinderance [2]. This poster highlights a rational design strategy of combining in silico and in vitro methods to engineer the transaminase enzyme with a minimal number of mutations, achieving high catalytic activity and high enantioselectivity. The wildtype TAm showed no detectable activity towards the ketone 2-acetylbiphenyl but upon introduction of two mutations detectable enzyme activity was observed. The reaction rate was improved a further 1716-fold with the rationally designed variant, that contained a further 5 mutations, producing the corresponding enantiomeric pure (S)-amine (enantiomeric excess (ee) value of \u3e99%)[3]. In addition, screening of in silico designed (R)-TAm mutant panels in resolution mode offered an attractive and efficient route for the preparation of problematic (S)-amines. A mutant was identified from the panels that gave complete resolution of the racemic amine (high substrate loading) to leave the desired enantiomer at a low enzyme loading fit for process development towards an economically viable scale up process. [1] R. C. Simon, et al, ACS Catal. 2014, 4(1) [2] F. Steffen-Munsberg, et al, ChemCatChem 2013, 5, (1) [3]D.F.A.R.Dourado et al, ACS Catal. 2016, 6 (11

Chemoenzymatic Probes for Detecting and Imaging Fucose-α(1-2)-galactose Glycan Biomarkers

The disaccharide motif fucose-α(1-2)-galactose (Fucα(1-2)Gal) is involved in many important physiological processes, such as learning and memory, inflammation, asthma, and tumorigenesis. However, the size and structural complexity of Fucα(1-2)Gal-containing glycans have posed a significant challenge to their detection. We report a new chemoenzymatic strategy for the rapid, sensitive detection of Fucα(1-2)Gal glycans. We demonstrate that the approach is highly selective for the Fucα(1-2)Gal motif, detects a variety of complex glycans and glycoproteins, and can be used to profile the relative abundance of the motif on live cells, discriminating malignant from normal cells. This approach represents a new potential strategy for biomarker detection and expands the technologies available for understanding the roles of this important class of carbohydrates in physiology and disease

A backward-mode optical-resolution photoacoustic microscope for 3D imaging using a planar Fabry-Pérot sensor

Optical-resolution photoacoustic microscopy (OR-PAM) combines high spatial resolution and strong absorption-based contrast in tissue, which has enabled structural and spectroscopic imaging of endogenous chromophores, primarily hemoglobin. This makes OR-PAM an important tool for preclinical vascular research. Conventional piezoelectric ultrasound transducers often need to be placed far away from the signal source due to their opacity, which results in reduced acoustic sensitivity. Optical ultrasound sensors are an alternative as their transparency allows them to be positioned close to the sample for minimal source-detector distances. In this work, a backward-mode OR-PAM system based on a planar Fabry-Pérot ultrasound sensor and coaxially aligned excitation and interrogation beams was developed. Two 3D imaging modes, using raster-scanning for enhanced image quality or continuous-scanning for fast imaging, were implemented and tested on a leaf skeleton phantom. In fast imaging mode, a scan-rate of 100,000 A-lines/s could be achieved. In raster-scanning mode, 3D images of a zebrafish embryo were acquired in vivo. The transparency of the FP sensor in the visible and near-infrared wavelength region makes it potentially suitable for combined functional and molecular imaging using OR-PAM and multi-photon fluorescence microscopy

Magnetic Anisotropy and Relaxation of Pseudotetrahedral [N2O2] Bis Chelate Cobalt II Single Ion Magnets Controlled by Dihedral Twist Through Solvomorphism

The methanol solvomorph 1 amp; 8201; amp; 8901; amp; 8201;2MeOH of the cobalt II complex [Co LSal,2 amp; 8722;Ph 2] 1 with the sterically demanding Schiff base ligand 2 [1,1 amp; 8242; biphenyl] 2 ylimino methyl phenol HLSal,2 amp; 8722;Ph shows the thus far largest dihedral twist distortion between the two chelate planes compared to an ideal pseudotetrahedral arrangement. The cobalt II ion in 1 amp; 8201; amp; 8901; amp; 8201;2MeOH exhibits an easy axis anisotropy leading to a spin reversal barrier of 55.3 amp; 8197;cm amp; 8722;1, which corresponds to an increase of about 17 amp; 8201; induced by the larger dihedral twist compared to the solvent free complex 1. The magnetic relaxation for 1 amp; 8201; amp; 8901; amp; 8201;2MeOH is significantly slower compared to 1. An in depth frequency domain Fourier transform FD FT THz EPR study not only allowed the direct measurement of the magnetic transition between the two lowest Kramers doublets for the cobalt II complexes, but also revealed the presence of spin phonon coupling. Interestingly, a similar dihedral twist correlation is also observed for a second pair of cobalt II based solvomorphs, which could be benchmarked by FD FT THz EP

Microsystem Technology for Ambient Assisted Living (AAL)

AbstractAAL is certainly an application area with sensor as well as actuator needs. Some of the requirements can be fulfilled by state of the art technology; some areas however still need a lot of R&D efforts for potential applications in homes. The contribution describes two areas of interest and actual development: One is the topic of robust fire detection; the other domain is fall detection. For both application areas one has to understand both the state of the art and the drawbacks of the current solutions. One can state clearly that there is a huge potential for the development of new microsystems. Still one has to keep in mind that usage in elderly homes also requires consent and cooperation of the users which is the focus of the user centered design principle

Is there a role of statins in the prevention of aortic biological prostheses degeneration

It has been recently observed that statins might slow the progression of aortic stenosis or sclerosis. Preliminary reports suggested a similar positive effect in reducing the degeneration of aortic valve bioprostheses even though this hypothesis should be further proven and supported by new data. In this review the present evidences of the possible effects of statins in this field are discussed

Gastric variceal bleeding caused by an intrahepatic arterioportal fistula that formed after liver biopsy: a case report and review of the literature

An intrahepatic arterioportal fistula is a rare cause of portal hypertension and variceal bleeding. We report on a patient with an intrahepatic arterioportal fistula following liver biopsy who was successfully treated by hepatectomy after unsuccessful arterial embolization. We also review the literature on symptomatic intrahepatic arterioportal fistulas after liver biopsy. A 48-year-old male with bleeding gastric varices and hepatitis B virus-associated liver cirrhosis was transferred to our hospital; this patient previously underwent percutaneous liver biopsies 3 and 6 years ago. Abdominal examination revealed a bruit over the liver, tenderness in the right upper quadrant, and splenomegaly. Ultrasonographic examination, computed tomography, and angiography confirmed an arterioportal fistula between the right hepatic artery and the right portal vein with portal hypertension. After admission, the patient suffered a large hematemesis and developed shock. He was treated with emergency transarterial embolization using microcoils. Since some collateral vessels bypassed the obstructive coils and still fed the fistulous area, embolization was performed again. Despite the second embolization, the collateral vessels could not be completely controlled. Radical treatment involving resection of his right hepatic lobe was performed. For nearly 6 years postoperatively, this patient has had no further episodes of variceal bleeding