Immobilised enzymes as drugs

Food and feed technology and biotechnology benefit from the use of immobilised enzymes. New low-cost enzyme carriers exhibiting high biocompatibility and response to external magnetic field can substantially improve the application potential of immobilised enzyme systems. Ferrofluid-modified spent grain was used as a low-cost, biocompatible and magnetically responsive carrier for the immobilisation of Candida rugosa lipase. Several immobilisation procedures were tested using both native and poly(ethyleneimine)-modified magnetic spent grain. Activity of immobilised lipase per unit mass of carrier, operational stability, time stability and Michaelis constant were compared. In general, magnetic spent grain modified with poly(ethyleneimine) bound a smaller amount of active lipase than unmodified magnetic spent grain, but the operational and storage stabilities of enzyme immobilised on poly(ethyleneimine)-modified carrier were very high. Ferrofluid-modified spent grain can be a promising low-cost magnetic carrier for enzyme immobilisation, applicable e.g. in food and feed technology and biotechnology.

The phenomenon of enzyme catalysis is discussed by the author in this chapter, and the role of the phenomenon in both industrial applications and biochemical processes. Enzymes are biochemical catalysts, and they are highly specific and efficient catalysts of reactions under mild conditions without being depleted. The chapter explores the enzyme structure, the active sites and substrate specificity, and this prevents the understanding of how the catalytic activity is determined by the molecular architecture. It also introduces the Michaelis-Menten kinetics, i.e. the relationship between substrate concentration and rate, and also emphasises such parameters as Vmax and Km and the use of enzymes in industrial processes, particularly food processing, pharmaceutical, biofuels, detergents and waste treatment and hence a sustainable and environmentally friendly process. The chapter places more emphasis on enzyme immobilization, enhancing stability, and optimization of processes that will ensure its successful implementation on an industrial level. The chapter provides an insight that is comprehensive as it relates biochemistry and industrial chemistry to enable the reader to understand how enzymatic catalysis could be used to increase the rate of reaction, reduce energy consumption, and mitigate the environmental effects. This is crucial to the learners who are strategizing to be experts in the field of biotechnology, biochemical engineering, and industrial enzymology.

With magnetic ferrite nanoparticles (FNPs) gaining interest in biotechnological fields and methacrylates being used as synthetic polymer for therapeutics loading and conjugation, we attempt to make novel magnetic composite by supercritical CO2 assisted entrapment of FNPs into in situ synthesized polymeric mesh of 2-amino ethyl methacrylate (AEMA) cross linked with methylene bis-acrylamide (MBA) at90±1 oC and pressure of 1200 psivia 2,2-azobisisobutyronitrile (AIBN) initiated radical polymerization. Particle thus obtained was characterized by using proton nuclear magnetic resonance (1H NMR), X-ray diffraction (XRD), thermal gravimetric-derivative thermogravimetric-differential thermal analysis (TG-DTGDTA), atomic force microscopy (AFM), and vibrating sample magnetometer (VSM). 1H NMR of Copolymer (without FNPs embedded) demonstrated distinct peaks verifying AEMA moieties flanked by MBA moieties with free amino group. Though the particle showed less saturation magnetization than that of as synthesized FNPs, it still maintained similar magnetic profile. AFM results showed average grain size of polymeric magnetic composites (PMCs) to be 80 nm with less agglomeration. TGA results verify the thermal stability of the compound upto 200 oC. In vivo acute cytotoxicity was profiled by administrating four different concentrations of FNPs, Copolymer and PMCs (FNPs embedded) into Sprague Dawley albino rat intraperitonally for 14 days and measuring various hematological, biochemical and serum enzymatic parameters along with histological examinations. Overall, PMCs showed no significance change in these parameters compared to normal saline administered control which signifies biocompatible nature of the composite. Hence, clean synthesis of FNPs embedded biocompatible amino functional magnetic composite has been achieved which holds potential in number of applications like drug loading, enzyme immobilizations, targeted therapy, etc.

Catalase immobilized in polypeptide/silica nanocomposites via emulsion and biomineralization with improved activities

A comparison of dehydration effects of V 2-antagonist (OPC-31260) on the inner ear between systemic and round window applications

The development of immobilized enzymes both for batch and continuous flow biocatalytic processes has gained significant traction in recent years, driven by the need for cost‐effective and sustainable production methods in the fine chemicals and pharmaceutical industries. Enzyme immobilization not only enables the recycling of biocatalysts but also streamlines downstream processing, significantly reducing the cost and environmental impact of biotransformations. This review explores recent advancements in enzyme immobilization techniques, covering both carrier‐free methods, entrapment strategies and support‐based approaches. At this regard, the selection of suitable materials for enzyme immobilization is examined, highlighting the advantages and challenges associated with inorganic, natural, and synthetic organic carriers. Novel opportunities coming from innovative binding strategies, such as genetic fusion technologies, for the preparation of heterogeneous biocatalysts with enhanced activity and stability will be discussed as well. This review underscores the need for ongoing research to address current limitations and optimize immobilization strategies for industrial applications.

Personalized medicine: Genetic risk prediction of drug response.

The research project is a subproject of an overall BMBF (German Federal Ministry of Education and Research) funded collaborative project. The joint project runs under the title "Preliminary Investigations of Microbial Load in the Middle Ear & Clinical Testing in Cholesteatoma Diagnosis & Therapy" or under the short title "BetterView". The aim of the overall study is an optimized visualization of medically relevant structures in the middle ear, especially in the context of cholesteatoma surgery. By extending the optical spectral range to the short-wave infrared, including novel contrast and visualization techniques, bacterial inflammation as well as other tissues relevant for surgery, such as bone, cartilage and soft tissue, will be visualized. The knowledge gained will be used to test and adapt the technical properties, handling and image quality of the SWIR microscope for everyday clinical use in order to establish intraoperative SWIR-assisted topographic analysis for the evaluation of biofilm infection of the cholesteatoma and relevant tissue types. The specific content of the subproject will be the first tissue examinations regarding their SWIR signature. In this context, different tissue types and cholesteatoma will be obtained intraoperatively, sectioned, stained, characterized and transferred to the project partners for visualization. Finally, direct comparisons can be made between microscopic tissue boundaries and SWIR-based imaging. The first tissue types have already been extracted and processed, enabling, among other things, differentiation between bone and cholesteatoma tissue in the SWIR range. The study results will largely serve to adapt the technical properties of the prototype SWIR microscope.

To determine the efficacy and safety profile of 6-month treatment with leflunomide 20mg daily in patients with acute rheumatoid arthritis (RA) receiving treatment from 197 office-based rheumatologists in France. This open-label, prospective, multicentre study included 378 ambulatory RA patients who received leflunomide at a loading dose of 100mg daily on days 1-3, followed by 20mg daily for 6 months. The primary efficacy endpoint was a >/=20% response according to the American College of Rheumatology criteria (ACR 20) after 6 months. Secondary efficacy criteria were a >/=50% response (ACR 50) and a >/=70% response (ACR 70), as well as disease activity score (DAS28) responses. Among the 407 selected patients, 378 patients were included in the study, all of whom were treated with leflunomide. Female patients made up 78.6% of the study population; the mean age was 57.7 +/- 12.0 years, and the mean disease duration was 9.7 +/- 8.5 years. At 6 months, the ACR 20 response rate was 48.2% (95% confidence interval [CI] 43-53%). ACR 50 and 70 response rates were 25.3% (95% CI 21.0-30.1) and 11.7% (95% CI 8.6-15.4%), respectively. According to the DAS28, 21.8% of patients had a good response, 39.9% a moderate response, and 38.2% were non-responders. The DAS28 response rate was thus 61.8% (95% CI 56.5-66.9%). Mean improvements in tender joint count were -5.6 +/- 7.4 (from baseline of 12.2 +/- 6.7), in swollen joint count were -4.2 +/- 5.7 (from baseline of 9.8 +/- 5.8), and in investigator's global assessment of RA disease activity were -20.2 +/- 25.1 (from baseline of 51.6 +/- 17.1). Treatment-related adverse events caused 15.9% of patients to discontinue the study prematurely. Serious adverse events possibly related to therapy were reported in 2.4% of patients. This 6-month study carried out under daily routine practice conditions in a typical sample of RA patients showed a favourable efficacy and safety profile for leflunomide 20mg daily. The study confirms the findings of the earlier phase II and III study programme in more selected patient samples.

Phenobarbital (PB) is the most widely used antiepileptic drug (AED) in the developing world and remains a popular choice in many industrialized countries. Meta-analyses of randomized controlled trials suggest that few differences in efficacy exist between PB and other established AEDs, but its possible deleterious cognitive and behavioral side effects remain a concern in the developed world. In contrast, high degrees of efficacy and tolerability in everyday clinical use have been demonstrated consistently in observational studies in developing countries. We propose that a pragmatic, comprehensive outcomes program be carried out, perhaps under the aegis of the Global Campaign Against Epilepsy, to optimize the conditions of the use of PB, so that more people around the world can benefit from this cost-effective medication and live more fulfilling lives.

This work is dedicated to development of the OCT system capable to visualize blood vessel network for everyday clinical use. Following problems were solved during the development: compensation of specific natural tissue displacements, induced by contact scanning mode and physiological motion of patients (e.g. respiratory and cardiac motions) and on-line visualization of vessel net to provide the feedback for system operator.

The goal of this retrospective study was to evaluate the development of visual acuity before and after recurrence treatment of neovascular age-related macular degeneration (AMD) in a university eye clinic with referring ophthalmologists. Data from patients with recurrent neovascular AMD who initially had been treated for neovascular AMD and followed by referring ophthalmologists were analyzed. An intravitreal recurrence treatment with ranibizumab using the same PrONTO scheme as used in the "upload" phase followed. Mean best corrected visual acuity (BCVA) of all 100 patients included in the study was - 0.61 ± 0.33 LogMAR before treatment and improved to - 0.36 ± 0.24 LogMAR (p < 0.001) after "upload" therapy. Mean central retinal thickness (CRT) was 291.5 ± 85.3μm before treatment and decreased to 200.1 ± 63.7μm after "upload" therapy (p < 0.001). At the time of recurrence the mean BCVA was - 0.63 ± 0.33 LogMAR and improved significantly to - 0.52 ± 0.28 LogMAR (p < 0.001) after recurrence treatment. At the time of recurrence the mean CRT was 281.2 ± 94.4μm and decreased significantly to 202.7 ± 59.9μm after recurrence treatment (p < 0.001). Retreatment criteria according to the PrONTO scheme showed good morphological and functional results in the patients with recurrent neovascular AMD treated but seemed to be defined too broadly for everyday clinical use with an irreversible loss under those conditions in cases of a recurrent episode. Accordingly, the latest recurrence criteria of the DOG/BVA/DOC recommendations should be applied.

Dental caries, a widespread oral health issue, necessitates early and accurate detection to ensure effective treatment and prevention. Traditional diagnostic methods often involve manual inspection and X-ray imaging, which can be time-consuming and subject to human error. This study introduces a cutting-edge approach by integrating machine learning with the YOLO (You Only Look Once) algorithm and leveraging the computational power of a Raspberry Pi to automate and enhance caries detection. The research focuses on developing a real-time, portable system for detecting dental caries from intraoral images using a Raspberry Pi. The YOLO algorithm, known for its efficiency in real-time object detection, is employed to train a model capable of identifying and classifying carious lesions in dental radiographs with high precision. This study aims to advance dental diagnostic capabilities by combining machine learning and embedded systems technology. The use of the YOLO algorithm with Raspberry Pi not only enhances the accuracy and speed of caries detection but also makes this advanced technology accessible and practical for everyday clinical use. Key Words: Dental caries, Open cv ,raspberry pi4 ,yoloV7

SUMMARYBackground: Currently available measures of the efficacy of acute migraine medications are not frequently used in primary care. They may be too burdensome and complicated for routine use.Objectives: To design and test a new, easy to use, 4-item assessment tool, the Migraine Assessment of Current Therapy (Migraine-ACT) questionnaire for use by clinicians, to quickly evaluate how a recently prescribed acute medication is working, and to identify patients who require a change of their current acute treatment.Methods: A 27-item Migraine-ACT questionnaire was developed by an international advisory board of headache specialists. Questions were formulated in four domains: headache impact, global assessment of relief, consistency of response and emotional response. All these are clinically important measures of migraine severity and treatment outcome. All questions were dichotomous and answered by yes or no. Patients (n = 185) attending secondary care headache clinics who were diagnosed with migraine according to International Headache Society criteria entered a multinational, prospective, observational study to investigate the test–retest reliability and construct validity of the 27-item Migraine-ACT. Patients completed the Migraine-ACT on two occasions, separated by a 1-week interval, and test–retest reliability was assessed by Pearson product moment and Spearman rank measures. Construct validity was assessed by correlating patients’ answers to the 27-item Migraine-ACT with those to other questionnaires (individual domains and total scores) conceptually related to it; the Short-Form 36 quality of life questionnaire (SF-36), the Migraine Disability Assessment (MIDAS) questionnaire and the Migraine Therapy Assessment Questionnaire (MTAQ). Discriminatory t-tests were used to identify the four Migraine-ACT questions (one in each domain) which discriminated best between the domains of the SF-36, MIDAS, and MTAQ. These four items constituted the final 4-item Migraine-ACT.Results: The test–retest reliability of the 27 Migraine-ACT questions ranged from good to excellent, and correlation coefficients were highly significant for all items. The consistency of reporting the yes and no answers was also excellent. Correlations of Migraine-ACT items with SF-36 and MIDAS items and SF-36, MIDAS and MTAQ total scores indicated that the following were the most discriminating items, in the respective four domains, and constitute the final Migraine-ACT questionnaire:•Consistency of response: Does your migraine medication work consistently, in the majority of your attacks?•Global assessment of relief: Does the headache pain disappear within 2 h?•Impact: Are you able to function normally within 2 h?•Emotional response: Are you comfortable enough with your medication to be able to plan your daily activities?The 4-item Migraine-ACT was shown to be highly reliable (Spearman/Pearson measure r = 0.82). The individual questions, and the total 4-item Migraine-ACT score, showed good correlation with items of the SF-36, MIDAS and MTAQ questionnaires, particularly with the total MTAQ and SF-36 scores.Conclusions: The 4-item Migraine-ACT questionnaire is an assessment tool for use by primary care physicians to identify patients who require a change in their current acute migraine treatment. It is brief and simple to complete and score, and has demonstrated reliability, accuracy and simplicity. Migraine-ACT can therefore be recommended for everyday clinical use by clinicians.

Es handelt sich hierbei um ein Update der im Frühjahr 2017 erstmals beschriebenen Qualitätskriterien und strukturellen Voraussetzungen für Cardiac Arrest Zentren auf Basis der ersten Zertifizierungen und Erfahrungen. Die Kriterien wurden angepasst und konkretisiert und zum Teil zur Umsetzbarkeit im klinischen Alltag neu definiert.