The significance of charged residues for the target-cell binding, potency and specificity of pediocin-like bacteriocins has been studied by site-directed mutagenesis of sakacin P. Most of the charged residues are located in the N-terminal half, which is thought to mediate the initial binding of these bacteriocins to target cells through electrostatic interaction. All the mutated peptides in which the net positive charge was reduced by one (by replacing a charged residue with threonine) exhibited reduced binding to target cells and a 2-15-fold reduction in potency. The least deleterious of these mutations was the removal of the positive charge in position 8 (H8T). This mutation was, in fact, less deleterious than the conservative His to Lys mutation, indicating that the positive charge in position 8 per se is not of major importance. Somewhat more deleterious was the removal of positive charges at the N- and C-terminal ends (K1T, K43T). Most deleterious was the elimination of the positive charge at positions 11 and (but to a lesser extent) 12, demonstrating the importance of the cationic patch in the middle of the N-terminal half of pediocin-like bacteriocins. Mutated peptides in which the net positive charge was increased by one were also constructed. Some of these exhibited increased cell binding and a potency that was the same as (44K, i.e. an extra positive charge at the C-terminus), or somewhat greater (T20K) than, that of sakacin P, whereas others (0K, i.e. an extra positive charge at the N-terminus) had reduced potency. Sakacin P contains only one negatively charged residue (Asp17). This negative charge and its orientation in space were crucial for activity, since the Asp to Asn mutation and (especially) the conservative Asp to Glu mutation were deleterious. Mutations that made the peptide less cationic had, overall, less effect on the potency toward the Carnobacterium piscicola strain than on the potency toward the three other strains tested, whereas the opposite was the case for mutations that made the peptide more cationic. Thus, charged residues in the N-terminal half may - apparently via the initial electrostatic binding of the bacteriocin to target cells - influence the target-cell specificity.
Uvod: U našoj studiji istraživali smo povezanost između cijene i djelotvornosti antimikrobika koji se primjenjuju na hirurškom odjelu. Na osnovu provedenih analiza željeli smo da napravimo vlastite zaključke o vrijednostima ovog modela analize u određenom periodu. Materijal i metoda: Studija se sastojala iz dva dijela: retrospektivnog (n=60) i prospektivnog (n=60). U periodu od jedne godine mi smo istraživali cijenu liječenja (farmakoterapija) na hirurškom odjelu. Analizirali smo primijenjene lijekove (prosječna dnevna doza) i izračunani smo potrošnju lijekova na osnovu definisane dnevne doze (DDD) kao i ukupnu cijenu primijenjene farmakoterapije. U prospektivnom dijelu istraživanja primijenili smo preporuke savremenih terapijskih vodica u određenim indikacijama - terapija infekcija i hirurška profilaksa. Analiza primijenjene terapije rađena je u statističkim programima SigmaStat 2.03 i Excel 2000 i na osnovu komparativne analize retrospektivnog i prospektivnog perioda istraživali smo efekat primjene farmakoterapijskih vodica na smanjenje ukupne cijene koštanja farmakoterapije. Rezultati: Naši rezultati pokazali su da je prosječna razlika između cijena primijenjenih lijekova u toku jednog bolničkog dana (BO dan) manja za 2,756 KM (smanjenje za 23,5%) u prospektivnom dijelu studije. U prospektivnom dijelu studije dokazali smo da primjenom savremenih preporuka o racionalnoj farmakoterapiji možemo smanjiti cijenu liječenja. Zaključak: Različite farmakoekonemske metode analize primjene lijekova sa kontinuiranim praćenjem savremenih farmakoterapijskih trendova u sklopu terapijskih vodica mogu nam pomoći da uskladimo potrebe bolesnika za pravilnim načinima liječenja i mogućosti društva u izdvajanju sredstava za farmakoterapiju.
No abstract available.
Direct monitoring by sensitive nucleic-acid tests would provide data accurately to measure the risk and to assess risk-reduction procedures. We adapted PCR method for investigation the incidence of HIV, hepatitis C virus and hepatitis B virus infections during last two (HBV, HCV) or three years (HIV) in Bosnia and Herzegovina. - For this PCR testing individual plasma samples were analyzed. Virus deoxyribonucleic acids were extracted by QIAamp nucleic acids extraction method. The HCV ribonucleic acid was extracted by High Pure Viral RNA Kit (Roche) also from plasma samples. We detected integrated form of HIV and HBV-viral DNA but in the case of HCV it was RNA from free viral particles present in the blood of patient. For HCV detection an additional reverse transcription step before PCR amplifications was performed. Amplified virus-specific sequences by specific complementary primers were detected by agarose-gel electrophoresis. - Using this validated methodology routine, we checked 184 persons on HIV infection from July 1998. up to the end of 2000. 8 (4.4%) of them were HIV-RNA positive. One of positive persons was a patient from Clinic of Infectious Diseases, other 7 HIV-RNA positive (6 injection drug users and 1 from promiscuity-risk group) were tested on their personal request. During 1999. and 2000 we performed 54 tests for identification HBV infected individuals and found 11 (20.4%) HBV positive persons. 7 of them were patients from Clinic of Gastroenterohaepathology, 1 from Paediatric Clinic and 3 from external medical institution. The HCV tests for the same period included 148 tested persons. 9 (6.1%) of them were HCV-RNA positive. It was 1 patient from Clinic of Infectious Diseases, 1 patient from Institute of Nephrology, 5 patients from Clinic of Gastroenterohaepathology and other 2 patients were from external medical institution. None of PCR-tested persons had HBV/HCV or other dual positivism. - HIV, HBV and HCV have been the viruses most intensively subjected to PCR analysis. It has been necessary to have an overview of incidence of infectious diseases caused by these viruses for a transition-state country such as BiH. In consideration of number of our population there is relatively high percentage of HIV, HCV and especially HBV positivism. It would be necessary to realize better transmission control preventing infections by these viruses in BiH. Those are the results of PCR diagnostics without serological investigations.
No abstract available.
No abstract available.
Magnetna rezonanca (MRI) i kompjuterizirana tomografija (CT) su komparirane u jednogodišnjoj retrospektivnoj studiji 17 pacijenata (9 muškog i 8 ženskog pola, prosječne dobi od 28,2 godina, 13 sa uputnom dijagnozom miastenija gravis i 4 perzistentni timus). Obje metode (CT i MRI) su potvrdile visoku senzitivnost i tačno identifikovale stanje timusa. CT nalazi su najčešće prikazali mekotkivnu masu ili nakupine masnog tkiva sa linearnim ili modularnim areama veće gustoće. MRI je obično prikazala aree nižeg intenziteta signala u TI i PD sekvencama, dok je u T2 signal bio nešto slabiji. TI i T2 Turbo Flash Breath Hold sekvence su se pokazale veoma korisnim u prikazu timusa sa mogućošću prikaza timusne kapsule. Radiološki nalazi su potvrđeni intraoperativno kod 12 pacijenata sa miastenijom gravis (11 pacijenata su imali timus perzistens i 1 pacijent timom). MRI i CT su veoma vrijedne komplementarne radiološke dijagnostičke metode vizuelizacije timusa. CT ima bolju prostornu rezoluciju i lakše prikazuje kalcifikacije. MRI jasno diferencira otočiće žljezdanog tkiva, osobito unutar masnog tkiva i timusnu kapsulu. Iako je MRI skuplja i pregled duže traje, ona je bez jonizirajućeg značenja i kao takva nije štetna.
No abstract available.
SUMMARY ∑ With the introduction of breath-hold techniques, magnetic resonance (MR) imaging has become an excellent diagnostic tool for the detection and characterization of benign and malignant liver lesions. Dynamic, gadolinium postcontrast studies as well tissue-specific contrast media highly improve the characterization of liver lesions. Multisection breath-hold techniques enable imaging of the entire region of interest in a single suspended respiration. MR-cholangiopancreatography allows for simultaneous analysis of biliary tree and pancreatic duct. The ability of various MR pulse sequences to display differences between normal and pathologic tissues is the basis of detection and characterization of focal and diffuse liver changes.
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