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Vírusellenes terápiás lehetőségek COVID–19 fertőzés kezelésére
Antiviral therapies for COVID-19 infections
Összefoglaló. A COVID–19-járvány egyre növekvő számú fertőzött betegének ellátása érdekében rövid időn belül szükség mutatkozott vírusellenes terápiás lehetőségekre. A gyors reagálás szempontját figyelembe véve erre a célra elsősorban más vírusok ellen már kifejlesztett vírusellenes szerek jöhetnek szóba. A magyar betegek ellátásbiztonsága szempontjából különösen fontos a hatóanyagok és gyógyszerkészítmények hazai gyártása. Ezt a cél tűzte ki a favipiravir, egy széles spektrumú antivirális hatóanyag hazai fejlesztése, amely sikeresen befejeződött, a gyógyszerkészítmény klinikai vizsgálata folyamatban van.
Summary. Increasing impact of COVID-19 on the healthcare system prompted the identification of potential antiviral therapies. Due to the immediate demand, known drugs were subjected to repositioning attempts. These drugs include agents inhibiting the viral entry into the host cells, drugs potentially blocking the release of the viral RNA from the endosomes, antivirals inhibiting the replication of the viral RNA and finally compounds that might prevent the assembly of the new virion. Since there is less experience with camostat and nafamostat, the entry inhibitors tested in Japan, and due to the ambiguous data collected with the endosome blocking chloroquine and hydroxyl-chloroquine, we focused on the actual antiviral treatment options for COVID-19 infections. In addition to favipiravir and remdesivir that were used early, at the onset of the pandemic, we discuss novel candidates including molnupiravir, a promising antiviral actually investigated in clinical trials. Considering the needs of Hungarian COVID patients and the security of supply as first priority, we selected favipiravir and developed a convenient process for the industry-scale production of the active pharmaceutical ingredient (API). At the end of this review we summarize the development and clinical investigation of favipiravir, a wide spectrum antiviral drug used for the treatment of mild and moderate COVID patients in Hungary in both ambulant and clinical settings. The Hungarian COVID Task Force set up two consortia, one for the development and the other for the clinical investigations of favipiravir. The objective of the favipiravir development consortium was to develop processes for the production of Favipiravir API and dosage forms. The consortium completed the pilot plant scale industrial production of the API and produced clinical samples for the upcoming trials. The selection and laboratory scale optimization of the synthesis route was performed at the Medicinal Chemistry Research Group of the Research Center for Natural Sciences. The laboratory scale synthesis was scaled up for pilot plant production at EVI plc and Gedeon Richter plc. GMP production was realized at the facilities of Gedeon Richter plc. Finished dosage forms were developed at Meditop Ltd who produced the clinical samples under GMP conditions. The clinical consortium is headed by the Hungarian section of the European Clinical Research Infrastructure Network (ECRIN) and organized two trials. One of these trials investigates favipiravir produced in Hungary while the other trial is performed with favipiravir produced in Japan. Both studies were approved by the Hungarian regulatory agency (OGYÉI) and are ongoing.
Abstract
Neutron activation analysis provides a useful clinical test to assess bone mass status in vivo. The neutron flux is obtained from Pu/Be sources and49Ca activity is measured by NaI detectors. For diagnostic value, the49Ca measurement is related to the mean value for normal subjects of the same body size. This normalized index, our CaBI, is used extensively to diagnose the bone loss associated with osteoporosis and to asses changes in bone mass with progression of disease and in response to treatments. Our facility operates at maximum capacity (35 tests/wk.). The hospital location and the dependability and ease of operation (provided by neutron sources) have facilitated extensive clinical use.
Abstract
The concentrations of Cl, K and Na were analyzed in human body fluids (whole blood and serum) using NAA, resulting in the first biochemical baseline values for the Brazilian population. These data permitted us a discussion about the advantages and limitations of using this analytical technique for clinical chemistry.
and 10 months after implantation. Later clinical investigations of pure Mg without steel screw showed successful results with children suffering from bone fracture (Fig. 3 ) . Thus, they recommended to use Mg implants in Bennett fractures, scaphoid
Abstract
1081 otorhinolaryngological articles originating from departments in the British Isles, published in 8 leading English language speciality journals from 1985–1989 were analysed to determine author and content trends. Articles were classified as clinical investigative, laboratory based, case report or review/editorial. The institution of origin, total number of authors and identity of the first three were recorded. There is evidence of an increase in published British otolaryngological research and in the extent of researcher collaboration.
Abstract
The radiochemical purity of MDP and HEDP has been determined by means of gel chromatography on Sephadex and thin layer chromatography on plastic foil silica gel. The comparison of the two radiopharmaceuticals shows equal level of complex formation with99mTc. The biodistribution demonstrated that the application of HEDP allows earlier scanning than MDP. MDP and HEDP show equal effectivity during the clinical investigations. There is no significant difference in the radiochemical purity within six hours after the reconstitution of the freeze-dried kits. HEDP kit demonstrates shorter period of accumulation and equivalent complex formation levels, so it can be used in routine nuclear medicine diagnostics together with MDP kit.
Abstract
This work describes an in vivo neutron activation analysis facility for small samples, such as rats or human hand, using two 100 
g252Cf neutron sources. The irradiation area is a cylindrical space, of 12 cm diameter and about 15 cm length, with fairly uniform neutron flux distribution. Experimental data on the reproducibility, effects of volume and other conditions for in vivo measurements are given. Comparative atomic absorption data on calcium measurements on rats are reported. The facility is now used for animal experiments as well as human hand irradiations in clinical investigations involving calcium metabolism and bone diseases.
Abstract
The comparative pharmacokinetic study of PAHIDA-99mTc p-(biscarboxymethyl)-aminomethylcarbaminohipuric acid, MAG3-99mTc (mercaptoacetyltrigly cine) and DTPA-99mTc (diethylenetriaminepentaacetate) was made by measurement of biodistribution, blood clearance, volume distribution, half-lives of distribution and elimination, and other relevant parameters. The percentage of protein binding was determined too, by the methods of dialysis and precipitation. These results were used to calculated the constants and rates of protein binding. The results of biodistribution show that MAG3-99mTc exibits a higher in the same time interval. The present work also reports results of clinical investigation of PAHIDA-99mTc.
Background
Sex addiction is a disorder that can have serious adverse functional consequences. Treatment effectiveness research for sex addiction is currently underdeveloped, and interventions are generally based on the guidelines for treating other behavioral (as well as chemical) addictions. Consequently, there is a need to clinically evaluate tailored treatments that target the specific symptoms of sex addiction. It has been proposed that second-generation mindfulness-based interventions (SG-MBIs) may be an appropriate treatment for sex addiction because in addition to helping individuals increase perceptual distance from craving for desired objects and experiences, some SG-MBIs specifically contain meditations intended to undermine attachment to sex and/or the human body. The current study conducts the first clinical investigation into the utility of mindfulness for treating sex addiction.
Case presentation
An in-depth clinical case study was conducted involving an adult male suffering from sex addiction that underwent treatment utilizing an SG-MBI known as Meditation Awareness Training (MAT). Following completion of MAT, the participant demonstrated clinically significant improvements in addictive sexual behavior, as well as reductions in depression and psychological distress. The MAT intervention also led to improvements in sleep quality, job satisfaction, and non-attachment to self and experiences. Salutary outcomes were maintained at 6-month follow-up.
Discussion and conclusion
The current study extends the literature exploring the applications of mindfulness for treating behavioral addiction, and findings indicate that further clinical investigation into the role of mindfulness for treating sex addiction is warranted.
MicroRNAs (miRNAs) are a recently discovered class of small, non-coding RNAs which do not code proteins. MiRNAs regulate gene expression by inhibiting protein translation from the messenger RNA. MiRNAs may function in networks, forming a complex relationship with diseases. Furthermore, specific miRNAs have significant correlation with diseases of divergent origin. After identification of disease-associated miRNAs, their tissue expression could be altered in a beneficial way by inhibiting or mimicking their effects. Thus, modifying the expression of miRNAs is a potential future gene-therapeutic tool to influence post-transcriptional regulation of multiple genes in a single therapy. In this review we introduce the biogenesis, mechanism of action and future aspects of miRNAs. Research on the post-transcriptional regulation of gene expression by miRNA may reshape our understanding of diseases and consequently may bring new diagnostic markers and therapeutic agents. Therapeutic use of miRNAs is already under clinical investigation in RNA interference trials.
