Regional status,epidemiology and impact of Taenia solium cysticercosis in Western and Central Africa

In West Africa, Taenia solium cysticercosis in both pigs and man has been reported in Benin, Burkina-Faso, Ghana, Ivory Coast, Senegal and Togo, and although official data are lacking, T. solium is anticipated to be present in most of the pig-raising regions of other West African countries as well. In some regions of Nigeria, the prevalence of porcine cysticercosis and human taeniosis is quite high (20.5 and 8.6%, respectively). Surprisingly, however, no cases of human cysticercosis have been reported, although epilepsy is very common. Large epidemiological surveys have only been carried out in Togo and Benin, where the prevalence of human cysticercosis was 2.4 and 1.3%, respectively. In Central Africa, porcine and human cysticercosis are (hyper)-endemic in Rwanda, Burundi, the Democratic Republic of Congo and Cameroon. The parasite also has been reported in pigs in Chad and Angola. Cysticercosis has been shown to be one of the major causes of epilepsy in Cameroon with figures as high as 44.6%. Cameroon is one of the few countries where the taeniosis-cysticercosis complex has been examined more in detail. In the Western province of Cameroon large scale surveys have shown that active cysticercosis is present in 0.4-3% of the local population and in 11% of the village pigs. However, the prevalence of adult T. solium was only 0.1%, which underscores the frequency of the T. solium paradox. Based on the available information, a very conservative economic estimate indicates that the annual losses due to porcine cysticercosis in 10 West and Central African countries amount to about 25 million Euro. The financial losses due to human cysticercosis are very difficult to estimate, but are certainly exceeded by the social impact of the disease, especially because of the particular perception of epilepsy in many African communities. It is concluded that the true prevalence of T. solium cysticercosis in pigs and humans in Central and West Africa remains underestimated because of unreliable slaughterhouse data and the lack of awareness and diagnostic facilities in the public health sector.     

Controlled release of chlorhexidine antiseptic from microporous amorphous silica applied in open porosity of an implant surface

Amorphous microporous silica (AMS) serving as a reservoir for controlled release of a bioactive agent was applied in the open porosity of a titanium coating on a Ti-6Al-4V metal substrate. The pores of the AMS emptied by calcination were loaded with chlorhexidine diacetate (CHX) via incipient wetness impregnation with CHX solution, followed by solvent evaporation. Using this CHX loaded AMS system on titanium substrate sustained release of CHX into physiological medium was obtained over a 10 day-period. CHX released from the AMS coating was demonstrated to be effective in killing planktonic cultures of the human pathogens Candida albicans and Staphylococcus epidermidis. This surface modification of titanium bodies with AMS controlled release functionality for a bioactive compound potentially can be applied on dental and orthopaedic implants to abate implant-associated microbial infection.     

A two‐step one‐pot radiosynthesis of the potent dopamine D2/D3 agonist PET radioligand [11C]MNPA

(R)‐(?)‐2‐[¹¹C]Methoxy‐N‐n‐propylnorapomorphine ([¹¹C]MNPA ([¹¹C]2)) is an agonist radioligand of interest for imaging D₂/D₃ receptors in vivo. Here we sought to develop an improved radiosynthesis of this radioligand. Reference 2 was synthesized in nine steps with an overall yield of about 5%, starting from codeine. Trimethylsilyldiazomethane proved to be a practical improvement in comparison to diazomethane in the penultimate methylation step. A protected precursor for radiolabeling ((R)‐(?)‐2‐hydroxy‐10,11‐acetonide‐N‐n‐propylnoraporphine, 4) was prepared from (R)‐(?)‐2‐hydroxy‐N‐n‐propylnorapomorphine (1) in 30% yield. [¹¹C]2 was prepared from 4 via a two‐step one‐pot radiosynthesis. The first step, methylation of 4 with [¹¹C]methyl triflate, occurred in quantitative radiochemical yield. The second step, deprotection of the catechol moiety with HCl and heat, yielded 60–90% of [¹¹C]2 giving an overall incorporation yield from [¹¹C]methyl triflate of 60–90%. In a typical run more than 1 GBq of [¹¹C]2, was produced from carbon‐11 generated from a 10‐min proton irradiation (16 MeV; 35 µA) of nitrogen–hydrogen target gas. The radiochemical purity of [¹¹C]2 was > 99% and specific radioactivity at the time of injection was 901±342 GBq/µmol (n=10). The total synthesis time was 35–38 min from the end of radionuclide production. The identity of [¹¹C]2 was confirmed by comparing its LC‐MS/MS spectrum with those of reference 2 and (R)‐(?)‐10‐methoxy‐2,11‐dihydroxy‐N‐n‐propylnoraporphine. Copyright © 2009 John Wiley & Sons, Ltd.     

Sutureless aortic valve replacement in multivalve procedures

BackgroundDespite the rapid expansion of transcatheter approaches for aortic valve implantation, surgical aortic valve replacement remains the treatment of choice in patients presenting with multiple valvular heart disease. We sought to review our clinical experience with sutureless aortic valve replacement (SU-AVR) in the setting of multivalve procedures, addressing the postoperative outcomes and technical challenges.MethodsBetween December 2019 and December 2020, 20 consecutive high-risk patients at our institution underwent SU-AVR and concomitant mitral valve procedure for various indications.ResultsThe mean age of the patients at operation was 72.6±9.3 years. Fifty five percent of the patients (n=11) presented with moderate to severe symptomatic aortic valve stenosis, while 35% (n=7) suffered from severe aortic regurgitation. All patients had concomitant moderate to severe mitral valve disease, including regurgitation in 95% (n=19) and stenosis in 25% (n=5). Mean logistic EuroSCORE was 34.3%±24.7%. Cardiopulmonary bypass and cross-clamp times were 101 (88.0–123) minutes and 67.5 (51.7–85.2) minutes, respectively. Optimal sutureless aortic valve prosthesis device success was achieved in 20 patients (100%). One patient (5%) required permanent pacemaker implantation. Thirty-day mortality was 10% and no strokes were detected.ConclusionsSU-AVR is a safe and feasible surgical alternative to conventional procedures in patients presenting with multiple valvular heart disease. It provides excellent hemodynamic performance with low risk of paravalvular leakage and low transvalvular gradients, whilst simplifying the surgical procedure. Precise sizing and positioning of the valve prostheses is crucial to ensure optimal postoperative outcome.     

Synthesis and biological evaluation of 3-aryl-3-(4-phenoxy)-propionic acid as a novel series of G protein-coupled receptor 40 agonists

High-throughput screening of a subset of the J&J compound library containing the carboxylic acid functional group uncovered a bromophenyl derivative as a moderate potent GPR40 agonist. Chemical elaboration of this bromophenyl led to the discovery of a novel series of GPR40 agonists with submicromolar potency. Among them, 22 and 24 behaved as full agonists when compared to the endogenous GPR40 ligand linolenic acid in a functional Ca+2 flux assay in HEK cells expressing GPR40 receptor. Several GPR40 agonists have also demonstrated the ability to induce glucose-mediated insulin secretion in the mouse MIN6 pancreatic beta-cell line. Our data supports the hypothesis that GPR40 may play an important role in fatty acid-mediated glucose-dependent insulin secretion. Compound 22 exhibited good pharmacokinetic profile in rat and may serve as a good candidate for in vivo study and may help to determine if GPR40 agonists would be beneficial in the treatment of type II diabetes.     

A new lupus anticoagulant neutralization test based on platelet-derived vesicles

We here present an easily standardizable and reproducible procedure which clearly separates lupus anticoagulants (LA) from coagulation factor inhibitors. This new LA neutralization test makes use of platelet-derived microvesicles which were prepared as follows: gel-filtered platelets (4 x 10(5)/microliters) were incubated with 60 microM of the calcium ionophore A23187 for 20 min at 37 degrees C. The vesicles were separated from the platelet aggregates by centrifugation at 1000 g for 10 min. The vesicle containing supernatant was then spun down at 15,000 g for 15 min, lyophilized and stored at -20 degrees C until used. The vesicles were resuspended in plasma from normal individuals, from patients with LA activity, from patients with factor VIII inhibitors, from patients with congenital factor deficiencies and from patients receiving oral anticoagulants or intravenous heparin. A kaolin clotting time was performed in the absence (KCT) or presence of these vesicles (KCTves) and the ratios of these times to their respective mean normal times were calculated. Segregation of LA patients from all remaining patients except heparinized ones could be made with a high degree of accuracy. A thrombin time was needed to separate LA from heparinized patients. The method was highly reproducible and only minor (negligible) differences in potencies were observed between different vesicle preparations. Both the intra-batch and the inter-batch coefficients of variations on the KCTves were lower than 6%.