Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking

Mátrix-asszisztált lézer deszorpciós, ionizaciós, repülési idő mérésen alapuló tömegspektrometria speciális alkalmazása a klinikai mikrobiológiai diagnosztika területen

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry as a new possibility for rapid identification of bacteria and fungi revolutionized the clinical microbiological diagnostics. It has an extreme importance in the routine microbiological laboratories, as identification of the pathogenic species rapidly will influence antibiotic selection before the final determination of antibiotic resistance of the isolate. The classical methods for identification of bacteria or fungi, based on biochemical tests, are influenced by many environmental factors. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry is a rapid method which is able to identify a great variety of the isolated bacteria and fungi based on the composition of conserved ribosomal proteins. Recently several other applications of the method have also been investigated such as direct identification of pathogens from the positive blood cultures. There are possibilities to identify bacteria from the urine samples in urinary tract infection or from other sterile body fluids. Using selective enrichment broth Salmonella sp from the stool samples can be identified more rapidly, too. The extended spectrum beta-lactamase or carbapenemase production of the isolated bacteria can be also detected by this method helping the antibiotic selection in some cases. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry based methods are suitable to investigate changes in deoxyribonucleic acid or ribonucleic acid, to carry out rapid antibiotic resistance determination or other proteomic analysis. The aim of this paper is to give an overview about present possibilities of using this technique in the clinical microbiological routine procedures. Orv. Hetil., 2014, 155(38), 1495-1503

Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary

Skeletal remains of two Neanderthal individuals, a 25-35 year-old woman and a 3-4 year-old child, were discovered in a Subalyuk Cave in North-Eastern Hungary. Radiocarbon dating of the female and child remains revealed an age of 39,732-39,076 and 36,117-35,387 cal BP, respectively. Paleopathological studies of these Neanderthal remains revealed probable evidence of skeletal mycobacterial infection, including in the sacrum of the adult specimen and the endocranial surface of the child's skull. Application of PCR amplification to the juvenile cranium and a vertebra gave a positive result (IS6110) for tuberculosis, backed up by spoligotyping. Lipid biomarker analyses of the same two specimens revealed definitive signals for C32 mycoserosates, a very characteristic component of the Mycobacterium tuberculosis complex (MTBC). A vertebra from the adult provided weak evidence for mycocerosate biomarkers. The correlation of probable skeletal lesions with characteristic amplified DNA fragments and a proven lipid biomarker points to the presence of tuberculosis in these Neanderthals. In particular, the closely similar biomarker profiles, for two distinct juvenile cranial and vertebral bones, strengthen this diagnosis. </p

Thromboangitis obliterans agyi manifesztációja

Thromboangiits obliterans (Buerger's disease) is a non-atherosclerotic, segmental inflammatory and obliterative disease affecting small and medium sized arteries and veins. The etiology is still unknown, but it is in close relationship with tobacco use. Symptoms begin under the age of 45 years and the undulating course is typical. Patients usually present with acute and chronic ischemic or infectious acral lesions. Diagnosis is usually based on clinical and angiographic criteria and it is important to exclude autoimmune disease, thrombophilia, diabetes, and proximal embolic sources. Even though Buerger's disease most commonly involves the arteries of the extremities, the pathologic findings sometimes affect the cerebral, coronary and internal thoracic, renal and mesenteric arteries as well. The authors present the history of a patient with known Buerger's disease and acute ischemic stroke. Brain imaging detected acute and chronic ischemic lesions caused by middle cerebral non-atherosclerotic arteriopathy on the symptomatic side. Other etiology was excluded by detailed investigations. Orv. Hetil., 2016, 157(30), 1207-1211

Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives

(−)-Cannabidiol (CBD) and (−)-cannabigerol (CBG) are two major non-psychotropic phytocannabinoids that have many beneficial biological properties. However, due to their low water solubility and prominent first-pass metabolism, their oral bioavailability is moderate, which is unfavorable for medicinal use. Therefore, there is a great need for appropriate chemical modifications to improve their physicochemical and biological properties. In this study, Mannich-type reaction was used for the synthetic modification of CBD and CBG for the first time, and thus fifteen new cannabinoid derivatives containing one or two tertiary amino groups were prepared. Thereafter the antiviral, antiproliferative and antibacterial properties of the derivatives and their effects on certain skin cells were investigated. Some modified CBD derivatives showed remarkable antiviral activity against SARS-CoV-2 without cytotoxic effect, while synthetic modifications on CBG resulted in a significant increase in antiproliferative activity in some cases compared to the parent compound

Regional, sex, and age differences in diagnostic testing among participants in the NAVIGATE-ESUS trial

Background and aim: The diagnosis of embolic stroke of undetermined source (ESUS) is based on excluding other more likely stroke etiologies, and therefore diagnostic testing plays an especially crucial role. Our objective was to compare the diagnostic testing by region, sex, and age among the participants of NAVIGATE-ESUS trial. Methods: Participants were grouped according to five global regions (North America, Latin America, Western Europe, Eastern Europe and East Asia), age (&lt;60, 60–74, and &gt;75 years), and sex. Frequencies of each diagnostic test within areas of echocardiography, cardiac rhythm monitoring, and arterial imaging were described and compared across groups. A multivariable logistic regression model for each diagnostic test was fit to assess the independent influence of each of region, age, and sex and likelihood of testing. Results: We included 6985 patients in the analysis (918 from North America; 746 from Latin America; 2853 from Western Europe; 1118 from Eastern Europe; 1350 from East Asia). Average age (highest in Western Europe (69 years), lowest in Eastern Europe (65 years)), % females (highest in Latin America (44%) and lowest in East Asia (31%)), and use of each diagnostic test varied significantly across regions. Region, but not sex, was independently associated with use of each diagnostic test examined. Transesophageal echocardiography and either CT or MR angiogram were more often used in younger patients. Conclusion: Diagnostic testing differed by region, and less frequently by age, but not by sex. Our findings reflect the existing variations in global practice in diagnostic testing in ESUS patients

Lipid-membrán iskola a Szegedi Biológiai Központban = Lipid-membrane school at the Biological Research Center

Tisztelegve az elhúnyt Farkas Tibor akadémikus emlékének, a Lipid-Membán Iskola a Szegedi Biológiai Központban minden tekintetben végrehajtotta a pályázatban tervezett feladatait, teljesítette misszióját. Képes volt a meglévő tudás valamint eszközállomány összefogására, koncentrált és hatékony kihasználására. A közös munka eredményeképpen számos, stratégiailag igen jelentős fejlesztés vált lehetővé. Nagy számú új, eredeti tudományos eredmény (köztük több review, ill. könyv) publikációjára került ill. kerül még sor a program lezárását követően. Törekvéseink fénypontját jelzik az egymolekula követésére alkalmas mikroszkópiás laboratórium (nanotechnológiai alapú membrán kutatóhely, SzBK) ill. az első hazai lipidomikai vertikum (SzTE, SzBK ) teljes kiépítése. Kiemelendő, hogy a program célkitűzésének megfelelően a kutatásba számos hallgatót vontunk be. Szakdolgozatok ill. PhD disszertációk születtek a pályázat támogatásával. Aktivitásunk egyértelmű nemzetközi elismeréseképpen 2006-ban Magyarországon kerül megrendezésre a Nemzetközi Lipidtudományi Konferencia (ICBL) kollégáink rendezésében, Vígh László elnökletével. A Lipid-Membrán Iskola szegedi résztvevői az alap- és alkalmazott lipid és membrán kutatási eredményeik, valamint a kiépült együttműködéseik alapján sikeresen részévé váltak a Dél-Alföldi Neurobiológiai Tudásközpontnak. | Saluting to the memory of late Tibor Farkas, the Lipid-Membrane School in the Szeged Biological Research Center successfully accomplished its major goals and fulfilled its mission. The school became capable for bringing together the preexisting knowledges and resources, by effectively concentrate and exploit them. As a result of the common and complementary efforts, several highly important and ambicious projects have been implemented. As a result of these, high number of new, original publications, reviews indicated the success. Amongst of our most remarkable achievements, we should mention the foundation of the nanotech based single molecule microscopy technique, allowing the real-time monitoring of most various lipid-membrane events (BRC). We are also proud, that the first Hungarian lipidomics lab can start soon its operation (SzTE, BRC). Several students participated in our activity: prepared diploma work and PhD thesis. Best highlighting our successful activity, our colleaques will organize the next International Congress of Lipid Sciences (ICBL), chaired by Laszlo Vigh. Based on their basic and applied research related activities and cooperation, most of the participants of the peresently terminated Szeged Lipid-Membrane School have joined successfully the Szeged Neurobiological Knowledge Center