Browsing by Subject "ANTIBIOTICS"

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  • McVey, Alyssa; Bartlett, Sean; Kajbaf, Mahmoud; Pellacani, Annalisa; Gatta, Viviana; Tammela, Päivi; Spring, David R.; Welch, Martin (2020)
    Pseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C-2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents.
  • Mgbeahuruike, Eunice Ego; Stålnacke, Milla; Vuorela, Heikki; Holm, Yvonne (2019)
    Microbial resistance to currently available antibiotics is a public health problem in the fight against infectious diseases. Most antibiotics are characterized by numerous side effects that may be harmful to normal body cells. To improve the efficacy of these antibiotics and to find an alternative way to minimize the adverse effects associated with most conventional antibiotics, piperine and piperlongumine were screened in combination with conventional rifampicin, tetracycline, and itraconazole to evaluate their synergistic, additive, or antagonistic interactions against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The fractional inhibitory concentration index was used to estimate the synergistic effects of various combination ratios of the piperamides and antibiotics against the bacterial and fungal strains. Both piperine and piperlongumine showed synergistic effects against S. aureus when combined at various ratios with rifampicin. Synergistic interaction was also observed with piperine in combination with tetracycline against S. aureus, while antagonistic interaction was recorded for piperlongumine and tetracycline against S. aureus. All the piperamide/antibacterial combinations tested against P. aeruginosa showed antagonistic effects, with the exception of piperine and rifampicin, which recorded synergistic interaction at a ratio of 9:1 rifampicin/piperine. No synergistic interaction was observed when the commercial compounds were combined with itraconazole and tested against C. albicans. The results showed that piperine and piperlongumine are capable of improving the effectiveness of rifampicin and tetracycline. Dosage combinations of these bioactive compounds with the antibiotics used may be a better option for the treatment of bacterial infections that aims to minimize the adverse effects associated with the use of these conventional antibacterial drugs.
  • Vanic, Zeljka; Rukavina, Zora; Manner, Suvi; Fallarero, Adyary; Uzelac, Lidija; Kralj, Marijeta; Klaric, Daniela Amidzic; Bogdanov, Anita; Raffai, Timea; Virok, Dezso Peter; Filipovic-Grcic, Jelena; Skalko-Basnet, Natasa (2019)
    Background: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.
  • Lamut, Andraž; Cruz, Cristina D.; Skok, Žiga; Barančoková, Michaela; Zidar, Nace; Zega, Anamarija; Peterlin Mašič, Lucija; Ilaš, Janez; Tammela, Päivi; Kikelj, Danijel; Tomašič, Tihomir (2020)
    Bacterial DNA gyrase is an important target for the development of novel antibacterial drugs, which are urgently needed because of high level of antibiotic resistance worldwide. We designed and synthesized new 4,5,6,7-tetrahydrobenzo[d]thiazole-based DNA gyrase B inhibitors and their conjugates with siderophore mimics, which were introduced to increase the uptake of inhibitors into the bacterial cytoplasm. The most potent conjugate 34 had an IC50 of 58 nM against Escherichia coli DNA gyrase and displayed MIC of 14 mu g/mL against E. coli.tolC strain. Only minor improvements in the antibacterial activities against wild-type E. coli in low-iron conditions were seen for DNA gyrase inhibitor - siderophore mimic conjugates.
  • Mali, Juha; Mentula, Panu; Leppäniemi, Ari; Sallinen, Ville (2019)
    BackgroundDiverticular abscess diameter of 3-6cm is generally accepted as a cutoff determining whether percutaneous drainage is recommended in addition to antibiotics, but this is not based on high-quality evidence. The aim of this study was to analyze the treatment choices and outcomes of patients with diverticular abscesses.MethodsThis was a retrospective cohort study conducted in an academic teaching hospital functioning as a secondary and tertiary referral center. Altogether, 241 patients with computer tomography-verified acute left-sided colonic diverticulitis with intra-abdominal abscess were collected from a database containing all patients treated for colonic diverticulitis in our institution during 2006-2013. The main measured outcomes were need of emergency surgery and 30-day mortality, and these were compared between antibiotics only and percutaneous drainage groups. Treatment choices, including surgery, were also analyzed for all patients.ResultsAbscesses under 40mm were mostly treated with antibiotics alone with a high success rate (93 out of 107, 87%). In abscesses over 40mm, the use of emergency surgery increased and the use of antibiotics alone decreased with increasing abscess size, but the proportion of successful drainage remained at 13-18% regardless of the abscess size. There were no differences in failure rate, 30-day mortality, the need of emergency surgery, permanent stoma, recurrence, or length of stay in patients treated with percutaneous drainage vs. antibiotics alone, even when groups were adjusted for potential confounders.ConclusionsPercutaneous drainage as a treatment for large abscess does not seem to be superior to the treatment with only antibiotics.
  • Laulajainen-Hongisto, Anu; Aarnisalo, Antti A.; Jero, Jussi (2016)
    Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.
  • Ding, Yaping; Li, Wei; Correia, Alexandra; Yang, Yuyun; Zheng, Kai; Liu, Dongfei; Schubert, Dirk W.; Boccaccini, Aldo R.; Santos, Helder A.; Roether, Judith A. (2018)
    Electrospun hybrid scaffolds are an effective platform to deliver drugs site specifically for the prevention and treatment of diseases in addition to promote tissue regeneration because of the flexibility to load drugs therein. In the present study, electrospun hybrid scaffolds containing antibiotics were developed to support cellular activities and eliminate potential postoperative inflammation and infection. As a model drug, levofloxacin (LFX) was successfully incorporated into pure polyhydroxybutyrate/poly(epsilon-caprolactone) (PHB/PCL) scaffolds and PHB/PCL/sol-gel-derived silica (SGS) scaffolds. The influence of LFX on the morphology, mechanical performance, chemical structure, drug release profile, and antibacterial effect of the scaffolds was thoroughly and comparatively investigated. MG-63 osteoblast-like cell cultivation on both scaffolds certified that LFX inclusion did not impair the biocompatibility. In addition to the favorable cellular proliferation and differentiation, scaffolds containing both LFX and SGS displayed highly increased mineralization content. Therefore, the present multifunctional hybrid scaffolds are promising in tissue engineering applications.
  • Pereira, Ana P.; Antunes, Patricia; Willems, Rob; Corander, Jukka; Coque, Teresa M.; Peixe, Luisa; Freitas, Ana R.; Novais, Carla (2022)
    Chlorhexidine (CHX) is widely used to control the spread of pathogens (e.g., human/animal clinical settings, ambulatory care, food industry). Enterococcus faecalis, a major nosocomial pathogen, is broadly distributed in diverse hosts and environments facilitating its exposure to CHX over the years. Nevertheless, CHX activity against E. faecalis is understudied. Our goal was to assess CHX activity and the variability of ChlR-EfrEF proteins (associated with CHX tolerance) among 673 field isolates and 1,784 E. faecalis genomes from the PATRIC database from different sources, time spans, clonal lineages, and antibiotic-resistance profiles. The CHX MIC (MICCHX) and minimum bactericidal concentration (MBCCHX) against E. faecalis presented normal distributions (0.5 to 64 mg/L). However, more CHX-tolerant isolates were detected in the food chain and recent human infections, suggesting an adaptability of E. faecalis populations in settings where CHX is heavily used. Heterogeneity in ChlR-EfrEF sequences was identified, with isolates harboring incomplete ChlR-EfrEF proteins, particularly the EfrE identified in the ST40 clonal lineage, showing low MICCHX (= 500 mg/L). However, increased CHX use, combined with concentration gradients occurring in diverse environments, potentially selecting multidrug-resistant strains with different CHX susceptibilities, signals the importance of monitoring the trends of E. faecalis CHX tolerance within a One Health approach. IMPORTANCE Chlorhexidine (CHX) is a disinfectant and antiseptic used since the 1950s and included in the World Health Organization's list of essential medicines. It has been widely applied in hospitals, the community, the food industry, animal husbandry and pets. CHX tolerance in Enterococcus faecalis, a ubiquitous bacterium and one of the leading causes of human hospital-acquired infections, remains underexplored. Our study provides novel and comprehensive insights about CHX susceptibility within the E. faecalis population structure context, revealing more CHX-tolerant subpopulations from the food chain and recent human infections. We further show a detailed analysis of the genetic diversity of the efrEF operon (previously associated with E. faecalis CHX tolerance) and its correlation with CHX phenotypes. The recent strains with a higher tolerance to CHX and the multiple sources where bacteria are exposed to this biocide alert us to the need for the continuous monitoring of E. faecalis adaptation toward CHX tolerance within a One Health approach. Chlorhexidine (CHX) is a disinfectant and antiseptic used since the 1950s and included in the World Health Organization's list of essential medicines. It has been widely applied in hospitals, the community, the food industry, animal husbandry and pets.
  • Heß, Stefanie; Hiltunen, Teppo; Berendonk, Thomas U.; Kneis, David (2020)
    The horizontal transfer of plasmids is a key mechanism behind the spread of antibiotic resistance in bacteria. So far, transfer rate constants were measured for a variety of plasmids, donors and recipients. The employed strains typically had a long history in laboratories. Existing data are, therefore, not necessarily representative for real-world environments. Moreover, information on the inter-strain variability of plasmid transfer rates is scarce. Using a high-throughput approach, we studied the uptake of RP4 by various Escherichia coli recipients using Serratia marcescens as the donor. The recipient strains were isolated from human-borne sewage and river sediments. The rate constants of plasmid transfer generally followed a log-normal distribution with considerable variance. The rate constants for good and poor recipients (95 and 5% quantile) differed by more than three orders of magnitude. Specifically, the inter-strain variability of the rate constant was large in comparison to alterations induced by low-level antibiotic exposure. We did not find evidence for diverging efficiencies of plasmid uptake between E. coli recipients of different origin. On average, strains isolated from river bottom sediments were equally efficient in the acquisition of RP4 as isolates extracted from sewage. We conclude that E. coli strains persisting in the aquatic environment and those of direct human origin share a similar intrinsic potential for the conjugative uptake of certain plasmids. In view of the large inter-strain variability, we propose to work towards probabilistic modeling of the environmental spread of antibiotic resistance.
  • Cruz, Cristina D; Wrigstedt, Pauli; Moslova, Karina; Iashin, Vladimir; Mäkkylä, Heidi; Ghemtio, Leo; Heikkinen, Sami; Tammela, Päivi; Perea-Buceta, Jesus Enrique (2021)
    N-aryl-oxazolidinones is a prominent family of antimicrobials used for treating infections caused by clinically prevalent Gram-positive bacteria. Recently, boron-containing compounds have displayed intriguing potential in the antibiotic discovery setting. Herein, we report the unprecedented introduction of a boron-containing moiety such as an aryl boronic acid in the external region of the oxazolidinone structure via a chemoselective acyl coupling reaction. As a result, we accessed a series of analogues with a distal aryl boronic pharmacophore on the oxazolidinone scaffold. We identified that a peripheric linear conformation coupled with freedom of rotation and no further substitution on the external aryl boronic ring, an amido linkage with hydrogen bonding character, in addition to a para-relative disposition between boronic group and linker, are the optimal combination of structural features in this series for antimicrobial activity. In comparison to linezolid, the analogue comprising all those features, compound 20b, displayed levels of antimicrobial activity augmented by an eight-fold to a thirty-two-fold against a panel of Gram-positive strains, and a near one hundred-fold against Escherichia coli JW5503, a Gram-negative mutant strain with a defective efflux capability.
  • Kelleher, Meredith A.; Lee, Ji Yeon; Roberts, Victoria; Novak, Christopher M.; Baschat, Ahmet A.; Morgan, Terry K.; Novy, Miles J.; Räsänen, Juha P.; Frias, Antonio E.; Burd, Irina (2020)
    BACKGROUND: Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases. OBJECTIVE: This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes. STUDY DESIGN: Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (107 colony-forming units/mL, n=15), and intraamniotic infection plus azithromycin treatment (12.5 mg/kg twice a day intravenously, n=8) groups. At approximately 135 days' gestation (term=165 days), pulsed and color Doppler ultrasonography was used to obtain measurements of fetal hemodynamics (pulsatility index of umbilical artery, ductus venosus, descending aorta, ductus arteriosus, aortic isthmus, right pulmonary artery, middle cerebral artery and cerebroplacental ratio, and left and right ventricular cardiac outputs) and cardiac function (ratio of peak early vs late transmitral flow velocity [marker of ventricular function], Tei index [myocardial performance index]). These indices were stratified by amniotic fluid proinflammatory mediator levels and cardiac histology. RESULTS: Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P1.1) than in those with normal blood flow (P1.6, P CONCLUSION: Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.
  • Provenzani, Riccardo; San-Martin-Galindo, Paola; Hassan, Ghada; Legehar, Ashenafi; Kallio, Aleksi Onni Oskari; Xhaard, Henri; Fallarero, Adyary; Yli-Kauhaluoma, Jari (2021)
    Biofilms are multicellular communities of microorganisms that generally attach to surfaces in a self-produced matrix. Unlike planktonic cells, biofilms can withstand conventional antibiotics, causing significant challenges in the healthcare system. Currently, new chemical entities are urgently needed to develop novel anti-biofilm agents. In this study, we designed and synthesized a set of 2,4,5,6-tetrasubstituted pyrimidines and assessed their antibacterial activity against planktonic cells and biofilms formed by Staphylococcus aureus. Compounds 9e, 10d, and 10e displayed potent activity for inhibiting the onset of biofilm formation as well as for killing pre-formed biofilms of S. aureus ATCC 25923 and Newman strains, with half-maximal inhibitory concentration (IC50) values ranging from 11.6 to 62.0 mu M. These pyrimidines, at 100 mu M, not only decreased the number of viable bacteria within the pre-formed biofilm by 2-3 log(10) but also reduced the amount of total biomass by 30-50%. Furthermore, these compounds were effective against planktonic cells with minimum inhibitory concentration (MIC) values lower than 60 mu M for both staphylococcal strains. Compound 10d inhibited the growth of S. aureus ATCC 25923 in a concentration-dependent manner and displayed a bactericidal anti-staphylococcal activity. Taken together, our study highlights the value of multisubstituted pyrimidines to develop novel anti-biofilm agents.
  • Ouedrhiri, Wessal; Mechchate, Hamza; Moja, Sandrine; Baudino, Sylvie; Saleh, Asmaa; Al Kamaly, Omkulthom M.; Grafov, Andriy; Greche, Hassane (2022)
    Nowadays, the combination of molecules influences their biological effects, and interesting outcomes can be obtained from different component interactions. Using a mixture design method, this research seeks to simulate the efficacy of essential oil combinations against various bacteria and forecast the ideal combination. The chemical compositions of Myrtus communis, Artemisia herba-alba and Thymus serpyllum essential oils were analyzed using CG/MS. Then, the combined antibacterial effects were evaluated by testing mixture design formulations using the microdilution bioassay. The main compounds detected for M. communis essential oil were myrtenyl acetate (33.67%), linalool (19.77%) and 1,8-cineole (10.65%). A. herba-alba had piperitone as a chemotype, representing 85%. By contrast, the T. serpyllum oil contained thymol (17.29%), gamma-terpinene (18.31%) and p-cymene (36.15%). The antibacterial effect of the essential oils studied, and the optimum mixtures obtained were target strain-dependent. T. serpyllum alone ensured the optimal inhibition against S. aureus and E. coli, while a ternary mixture consisting of 17.1%, 39.6% and 43.1% of M. communis, A. herba-alba and T. serpyllum respectively, was associated with optimal inhibitory activity against B. subtilis. The outcome of this research supports the idea of the boosting effect of essential oil combinations toward better activities, giving better understanding of the usefulness of mixture designs for food, cosmetics, and pharmaceutical applications.
  • Aguilera-Correa, John Jairo; Fernandez-Lopez, Sara; Cunas-Figueroa, Iskra Dennisse; Perez-Rial, Sandra; Alakomi, Hanna-Leena; Nohynek, Liisa; Oksman-Caldentey, Kirsi-Marja; Salminen, Juha-Pekka; Esteban, Jaime; Cuadros, Juan; Puupponen-Pimia, Riitta; Perez-Tanoira, Ramon; Kinnari, Teemu J. (2021)
    Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.
  • Oksa, Marko; Haapanen, Aleksi; Marttila, Emilia; Snäll, Johanna (2022)
    Objective To evaluate the occurrence of surgical site infections and predisposing factors for these in simple mandibular fractures. Material and Methods A retrospective study of patients with fractures of the dentate part of the mandible included patients with intraorally treated simple fractures of the mandibular body, symphysis, and parasymphysis. The primary outcome variable was postoperative surgical site infection. Use of antibiotics, injury mechanism, fracture and surgery-related explanatory variables, patient-related variables and level of oral hygiene according to the modified Total Dental Index were evaluated. Results Of 254 patients with mandibular fractures, 107 were included in the final analysis. The infection group consisted of 18 patients (16.8%). Despite the high infection occurrence, significant differences were not found between antibiotic use or other studied variables and infection occurrence. Infections occurred mainly in patients without any specific explanatory factor for infection. Conclusion The notably high occurrence of surgical site infections despite antibiotic use after simple mandibular fracture surgery highlights the importance of perioperative tissue handling and local oral circumstances. It is also necessary to consider whether we generally accept the high risk of infection associated with the intraorally treated simple mandibular fractures.
  • Pelkonen, Tuula; Roine, Irmeli; Cruzeiro, Manuel Leite; Pitkäranta, Anne; Kataja, Matti; Peltola, Heikki (2011)
  • El Fellah, Samira; Duporte, Geoffroy; Siren, Heli (2017)
    Steroid hormones, botrydial, and inorganic ions were studied from cold and hot tap water samples with capillary electrophoresis techniques using UV detection. Identification of the steroids and botrydial was made with ultra-high -performance liquid chromatography (UHPLC) coupled to electrospray ionization orbitrap high-resolution mass spectrometry. Solid phase extraction with nonpolar and ion-exchange sorbents was needed to enrich the compounds for CE and UHPLC studies. The steroids identified from the drinking water samples were estradiol glucoside, androstenedione, testosterone, and progesterone. However, only progesterone could be quantified in both cold and hot tap water samples from Helsinki households. Its concentration varied from 0.031 ng/L to 0.135 ng/L and from 0.054 ng/L to 0.191 ng/L, respectively. Chloride and nitrate amounts were 25 mg/L. Calcium, potassium, magnesium, and sodium were 20, 1, 1, and 17 mg/L at the highest, respectively. Copper, iron, sulphate, and ammonium were below the methods concentration limits. Botrydial from Botrytis cinerea mould was identified in all drinking waters. In both cold and hot tap waters its concentration was 861-3900% higher than in a drilled well water that was also used as the household tap water. The mould was also confirmed by identification of its metabolite abscisic acid. (C) 2017 Elsevier B.V. All rights reserved.
  • Aly, Ashraf A.; El-Sheref, Essmat M.; Mourad, Aboul-Fetouh E.; Brown, Alan B.; Bräse, Stefan; Bakheet, Momtaz E. M.; Nieger, Martin (2018)
    Quinoline-2,4-diones reacted with 2-(2-oxo-1,2-dihydroindol-3-ylidene)malononitrile in pyridine to give 2'-amino-2,5'-dioxo-5',6'-dihydrospiro(indoline-3,4'-pyrano[3,2-c]quinoline)-3'-carbonitriles in good to excellent yields. The structures of all new products were proven using one- and two-dimensional NMR, IR, and mass spectral data, and in five cases X-ray structural analyses. The possible mechanism for the reaction is also discussed. [GRAPHICS] .
  • Yun, Jinhyeon; Olkkola, Satu; Hänninen, Marja-Liisa; Oliviero, Claudio; Heinonen, Mari (2017)
    This study investigated the effects of a single amoxicillin treatment of newborn piglets on the prevalence of hernias and abscesses until the age of nine weeks. We also studied whether the treatment was associated with growth and mortality, the need for treatment of other diseases, the proportions of ampicillin resistant coliforms and antimicrobial resistance patterns of intestinal Escherichia coli (E. coli). A total of 7156 piglets, from approximately 480 litters, were divided into two treatment groups: ANT (N = 3661) and CON (N = 3495), where piglets were treated with or without a single intramuscular injection of 75 mg amoxicillin one day after birth, respectively. The umbilical and inguinal areas of weaned pigs were palpated at four and nine weeks of age. At the same time, altogether 124 pigs with hernias or abscesses and 820 non -defective pigs from three pens per batch were weighed individually. Mortality and the need to treat piglets for other diseases were recorded. Piglet faecal samples were collected from three areas of the floors of each pen at four weeks of age. The prevalence of umbilical hernias or abscesses did not differ between the groups at four weeks of age, but it was higher in the CON group than in the ANT group at nine weeks of age (2.3% vs. 0.7%, P
  • Hess, Stefanie; Kneis, David; Virta, Marko; Hiltunen, Teppo (2021)
    The rapid spread of antibiotic resistance challenges modern medicine. So far, mechanistic and quantitative knowledge concerning the spread of resistance genes mainly relies on laboratory experiments with simplified setups, e.g. two strain communities. Thus, the transferability of the obtained process rates might be limited. To investigate the role of a diverse community concerning the dissemination of the multidrug resistance plasmid RP4, an Escherichia coli harboring RP4 invaded a microbial community consisting of 21 species. Changes in the community composition as well as plasmid uptake by community members were monitored for 22 days. Special focus was laid on the question of whether the observed changes were dependent on the actual invading donor isolate and the ambient antibiotic concentration. In our microcosm experiment, the community composition was primarily influenced by the given environmental variables and only secondarily by the particular invader E. coli. The establishment of resistance within the community, however, was directly dependent on the donor identity. The extent to which ambient conditions influence the spread of RP4 depended on the E. coli donor strain. These results emphasize that even within one species there are great differences in the ability to conquer an ecological niche and to spread antibiotic resistance.