scholarly journals The generality of post-antimicrobial treatment persistence of replicatively-attenuatedBorrelia burgdorferiin a mouse model

2019 ◽  
Author(s):  
Emir Hodzic ◽  
Denise M. Imai ◽  
Edlin Escobar
Keyword(s):  
Mouse Model ◽  
Antimicrobial Agents ◽  
Basic Feature ◽  
Antimicrobial Treatment ◽  
Therapy Failure ◽  
Treatment Persistence ◽  
Disease Resistant ◽  
C3h Mice ◽  
The Status ◽  
Long Time

ABSTRACTA basic feature of infection caused byBorrelia burgdorferi, the etiological agent of Lyme borreliosis, is that persistent infection is the rule, not the norm, in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge. There is growing experimental evidence that viable, but non-cultivable spirochetes persist following treatment with several different antimicrobial agents, then resurge after 12 months. The current study utilized the mouse model to evaluate if persistence and resurgence occur following antimicrobial treatment in a disease-susceptible (C3H/HeN) and disease-resistant (C57BL/6) mouse strain infected withB. burgdorferistrains N40 and B31, to confirm the generality of these phenomena. The status of infection was evaluated at 12 and 18-months after treatment. The results demonstrated that persistent spirochetes remain viable for up to 18 months following treatment, but divide slowly, thereby being tolerant to the effects of antimicrobial agents, as well as being non-cultivable. The phenomenon of persistence and resurgence in disease-susceptible C3H mice is equally evident in disease-resistant B6 mice, and not unique to any particularB. burgdorferistrain. The results also demonstrate that following antimicrobial treatment, both strains ofB. burgdorferi, N40 and B31, lose one or more small plasmids, resulting in attenuation. The biological relevance of attenuatedB. burgdorferispirochetes is probably inconsequential. The study demonstrated that non-cultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection.

scholarly journals Generality of Post-Antimicrobial Treatment Persistence of Borrelia burgdorferi Strains N40 and B31 in Genetically Susceptible and Resistant Mouse Strains

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Emir Hodzic ◽  
Denise M. Imai ◽  
Edlin Escobar
Keyword(s):  
Mouse Model ◽  
Borrelia Burgdorferi ◽  
Clinical Relevance ◽  
Antimicrobial Agents ◽  
Basic Feature ◽  
Antimicrobial Treatment ◽  
Mouse Strains ◽  
Resistant Mouse ◽  
Content Type ◽  
Disease Resistant

ABSTRACT A basic feature of infection caused by Borrelia burgdorferi, the etiological agent of Lyme borreliosis, is that persistent infection is the rule in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge. There is growing experimental evidence that viable but noncultivable spirochetes persist following treatment with several different antimicrobial agents. The current study utilized the mouse model to evaluate if persistence occurs following antimicrobial treatment in disease-susceptible (C3H/HeJ [C3H]) and disease-resistant (C57BL/6 [B6]) mouse strains infected with B. burgdorferi strains N40 and B31 and to confirm the generality of this phenomenon, as well as to assess the persisters’ clinical relevance. The status of infection was evaluated at 12 and 18 months after treatment. The results demonstrated that persistent spirochetes remain viable for up to 18 months following treatment, as well as being noncultivable. The phenomenon of persistence in disease-susceptible C3H mice is equally evident in disease-resistant B6 mice and not unique to any particular B. burgdorferi strain. The results also demonstrate that, following antimicrobial treatment, both strains of B. burgdorferi, N40 and B31, lose one or more plasmids. The study demonstrated that noncultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection. The clinical relevance of persistent spirochetes beyond 18 months following antimicrobial treatment requires further studies in other animal models.

Euratom and Brexit: Could the United Kingdom Maintain One Foot in the European Union? Current Scenarios and Future Prospects of British withdrawal from the EAEC

2018 ◽  
Vol 18 (2) ◽  
pp. 134-151
Author(s):  
Andrea Circolo ◽  
Ondrej Hamuľák
Keyword(s):  
European Union ◽  
United Kingdom ◽  
Independent Solution ◽  
Legal Regulation ◽  
The European Union ◽  
The United Kingdom ◽  
The Status ◽  
Long Time ◽  
Energy Community ◽  
The Impact

Abstract The paper focuses on the very topical issue of conclusion of the membership of the State, namely the United Kingdom, in European integration structures. The ques­tion of termination of membership in European Communities and European Union has not been tackled for a long time in the sources of European law. With the adop­tion of the Treaty of Lisbon (2009), the institute of 'unilateral' withdrawal was intro­duced. It´s worth to say that exit clause was intended as symbolic in its nature, in fact underlining the status of Member States as sovereign entities. That is why this institute is very general and the legal regulation of the exercise of withdrawal contains many gaps. One of them is a question of absolute or relative nature of exiting from integration structures. Today’s “exit clause” (Art. 50 of Treaty on European Union) regulates only the termination of membership in the European Union and is silent on the impact of such a step on membership in the European Atomic Energy Community. The presented paper offers an analysis of different variations of the interpretation and solution of the problem. It´s based on the independent solution thesis and therefore rejects an automa­tism approach. The paper and topic is important and original especially because in the multitude of scholarly writings devoted to Brexit questions, vast majority of them deals with institutional questions, the interpretation of Art. 50 of Treaty on European Union; the constitutional matters at national UK level; future relation between EU and UK and political bargaining behind such as all that. The question of impact on withdrawal on Euratom membership is somehow underrepresented. Present paper attempts to fill this gap and accelerate the scholarly debate on this matter globally, because all consequences of Brexit already have and will definitely give rise to more world-wide effects.

scholarly journals Upregulation of Vitamin C Transporter Functional Expression in 5xFAD Mouse Intestine

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 617
Author(s):  
Trevor Teafatiller ◽  
Christopher W. Heskett ◽  
Anshu Agrawal ◽  
Jonathan S. Marchant ◽  
Janet E. Baulch ◽  
...  
Keyword(s):  
Mouse Model ◽  
Functional Expression ◽  
Specific Protein ◽  
Glutathione Peroxidase 1 ◽  
Stress Response Genes ◽  
Nuclear Rna ◽  
The Status ◽  
5Xfad Mouse ◽  
Mouse Intestine ◽  
5Xfad Mice

The process of obtaining ascorbic acid (AA) via intestinal absorption and blood circulation is carrier-mediated utilizing the AA transporters SVCT1 and SVCT2, which are expressed in the intestine and brain (SVCT2 in abundance). AA concentration is decreased in Alzheimer’s disease (AD), but information regarding the status of intestinal AA uptake in the AD is still lacking. We aimed here to understand how AA homeostasis is modulated in a transgenic mouse model (5xFAD) of AD. AA levels in serum from 5xFAD mice were markedly lower than controls. Expression of oxidative stress response genes (glutathione peroxidase 1 (GPX1) and superoxide dismutase 1 (SOD1)) were significantly increased in AD mice jejunum, and this increase was mitigated by AA supplementation. Uptake of AA in the jejunum was upregulated. This increased AA transport was caused by a marked increase in SVCT1 and SVCT2 protein, mRNA, and heterogeneous nuclear RNA (hnRNA) expression. A significant increase in the expression of HNF1α and specific protein 1 (Sp1), which drive SLC23A1 and SLC23A2 promoter activity, respectively, was observed. Expression of hSVCT interacting proteins GRHPR and CLSTN3 were also increased. SVCT2 protein and mRNA expression in the hippocampus of 5xFAD mice was not altered. Together, these investigations reveal adaptive up-regulation of intestinal AA uptake in the 5xFAD mouse model.

scholarly journals Imidocarb Dipropionate Clears Persistent Babesia caballi Infection with Elimination of Transmission Potential

2009 ◽  
Vol 53 (10) ◽  
pp. 4327-4332 ◽  
Author(s):  
O. Nicolas Schwint ◽  
Massaro W. Ueti ◽  
Guy H. Palmer ◽  
Lowell S. Kappmeyer ◽  
Melissa T. Hines ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Animal Movement ◽  
Pcr Amplification ◽  
Antimicrobial Treatment ◽  
Transmission Risk ◽  
High Dose ◽  
Babesia Caballi ◽  
Transmission Potential ◽  
Imidocarb Dipropionate ◽  
Direct Inoculation

ABSTRACT Antimicrobial treatment of persistent infection to eliminate transmission risk represents a specific challenge requiring compelling evidence of complete pathogen clearance. The limited repertoire of antimicrobial agents targeted at protozoal parasites magnifies this challenge. Using Babesia caballi as both a model and a specific apicomplexan pathogen for which evidence of the elimination of transmission risk is required for international animal movement, we tested whether a high-dose regimen of imidocarb dipropionate cleared infection from persistently infected asymptomatic horses and/or eliminated transmission risk. Clearance with elimination of transmission risk was supported by the following four specific lines of evidence: (i) inability to detect parasites by quantitative PCR and nested PCR amplification, (ii) conversion from seropositive to seronegative status, (iii) inability to transmit infection by direct inoculation of blood into susceptible recipient horses, and (iv) inability to transmit infection by ticks acquisition fed on the treated horses and subsequently transmission fed on susceptible horses. In contrast, untreated horses remained infected and capable of transmitting B. caballi using the same criteria. These findings establish that imidocarb dipropionate treatment clears B. caballi infection with confirmation of lack of transmission risk either by direct blood transfer or a high tick burden. Importantly, the treated horses revert to seronegative status according to the international standard for serologic testing and would be permitted to move between countries where the pathogen is endemic and countries that are free of the pathogen.

scholarly journals Sustainable exploitation of temperate fish stocks

2009 ◽  
Vol 6 (1) ◽  
pp. 124-127 ◽  
Author(s):  
Henrik Sparholt ◽  
Robin M. Cook
Keyword(s):  
Species Interactions ◽  
Fishery Management ◽  
Regional Scale ◽  
Single Species ◽  
Fishing Effort ◽  
Theoretical Concept ◽  
Maximum Sustainable Yield ◽  
Production Model ◽  
The Status ◽  
Long Time

The theory of maximum sustainable yield (MSY) underpins many fishery management regimes and is applied principally as a single species concept. Using a simple dynamic biomass production model we show that MSY can be identified from a long time series of multi-stock data at a regional scale in the presence of species interactions and environmental change. It suggests that MSY is robust and calculable in a multispecies environment, offering a realistic reference point for fishery management. Furthermore, the demonstration of the existence of MSY shows that it is more than a purely theoretical concept. There has been an improvement in the status of stocks in the Northeast Atlantic, but our analysis suggests further reductions in fishing effort would improve long-term yields.

Antimicrobial Treatment of Acute Otitis Media

1994 ◽  
Vol 103 (5_suppl) ◽  
pp. 11-14 ◽  
Author(s):  
Daniel M. Canafax ◽  
G. Scott Giebink
Keyword(s):  
Hearing Loss ◽  
Otitis Media ◽  
Antimicrobial Agents ◽  
Acute Otitis Media ◽  
Antimicrobial Treatment ◽  
Speech Delay ◽  
Significant Morbidity ◽  
Antimicrobial Drugs ◽  
Etiologic Role ◽  
History Of

Episodes of acute otitis media frequently occur in childhood and are attended by significant morbidity, such as hearing loss and possible speech delay. Bacteria play an important etiologic role in the pathogenesis of otitis media; therefore, antimicrobial agents are the cornerstone in the treatment of this disease. Many antimicrobial choices are available for treating children with acute otitis media. To choose an antimicrobial for each patient, consideration must be given to the patient's age, history of otitis media episodes, and responses to previously used antimicrobial drugs, and the regional antimicrobial susceptibility of the otitis media pathogens.

Principles of Judicious Use of Antimicrobial Agents for Pediatric Upper Respiratory Tract Infections

PEDIATRICS ◽  
1998 ◽  
Vol 101 (Supplement_1) ◽  
pp. 163-165 ◽  
Author(s):  
Scott F. Dowell ◽  
S. Michael Marcy ◽  
William R. Phillips ◽  
Michael A. Gerber ◽  
Benjamin Schwartz
Keyword(s):  
Respiratory Tract ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
The United States ◽  
Antimicrobial Treatment ◽  
Antimicrobial Use ◽  
Upper Respiratory Tract ◽  
Oral Agents ◽  
Upper Respiratory ◽  
Tract Infections

This article introduces a set of principles to define judicious antimicrobial use for five conditions that account for the majority of outpatient antimicrobial use in the United States. Data from the National Center for Health Statistics indicate that in recent years, approximately three fourths of all outpatient antibiotics have been prescribed for otitis media, sinusitis, bronchitis, pharyngitis, or nonspecific upper respiratory tract infection.1Antimicrobial drug use rates are highest for children1; therefore, the pediatric age group represents the focus for the present guidelines. The evidence-based principles presented here are focused on situations in which antimicrobial therapy could be curtailed without compromising patient care. They are not formulated as comprehensive management strategies. For most upper respiratory infections that require antimicrobial treatment, there are several appropriate oral agents from which to choose. Although the general principles of selecting narrow-spectrum agents with the fewest side effects and lowest cost are important, the principles that follow include few specific antibiotic selection recommendations.

scholarly journals Micronuclei in blood lumphocytes of existing and former coal miners: evaluation of the effect of anthracosilicosis

2019 ◽  
Vol 17 (4) ◽  
pp. 57-64
Author(s):  
Vladimir G. Druzhinin ◽  
Svetlana V. Apalko ◽  
Elizaveta D. Baranova ◽  
Valentin P. Volobaev ◽  
Tatiana Yu. Drobchik ◽  
...  
Keyword(s):  
Coal Dust ◽  
Additional Contribution ◽  
Coal Miners ◽  
Genotoxic Effects ◽  
The Status ◽  
Long Time ◽  
Inflammatory Processes ◽  
Simultaneous Decrease ◽  
Genotoxic Risk ◽  
Cytogenetic Parameters

Background. The purpose of this study was to investigate the genotoxic risk in anthracosilicosis patients and in those with occupational exposure to coal dust. Materials and methods. We studied micronuclei (MN) and other cytogenetic lesions in blood lymphocytes in three groups of men comparable in age: 74 coal miners suffering from anthracosilicosis (AS), 41 healthy miners, and 70 control donors. Results. A significant increase in the frequency of MN was revealed with a simultaneous decrease in proliferative activity in samples of healthy and sick miners compared with the control. The level of MN in the lymphocytes of patients with AS significantly exceeded the corresponding indicator in the sample of healthy miners (1.22 0.05% versus 1.03 0.07%; p 0.01). The age of the subjects and the status of smoking did not have a significant effect on the frequency of cytogenetic parameters. Conclusion. AS in miners makes an additional contribution to the formation of DNA damage in lymphocytes. This contribution is probably due to oxidative stress accompanying inflammatory processes in pulmonary fibrosis. The results of the study also indicate the absence of differences in the frequency of MN when comparing subgroups of current and former miners. This means that the genotoxic effects in the lymphocytes of miners are able to persist for a long time after the termination of exposure by adverse factors in coal mining.

scholarly journals Morphology and distribution of the freshwater mussel Diplodon granosus, a rare and poorly understood species

2020 ◽  
Vol 50 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Igor Christo MIYAHIRA ◽  
Maria Cristina Dreher MANSUR ◽  
Daniel Mansur PIMPÃO ◽  
Sheyla Regina Marques COUCEIRO ◽  
Sonia Barbosa dos SANTOS
Keyword(s):  
South America ◽  
Freshwater Mussels ◽  
Freshwater Mussel ◽  
Wide Distribution ◽  
Large Area ◽  
The North ◽  
Coastal Rivers ◽  
The Status ◽  
Long Time

ABSTRACT Diplodon granosus was one of the first freshwater mussels to be described for South America. However, the status of the species was confusing for a long time, receiving different taxonomic treatments. In this paper, we redescribe the shell, with new data on the soft parts and information on the distribution and conservation of D. granosus, a rarely recorded species. The shell is thin, not inflated; the macrosculpture is composed only by granules that cover the whole shell, not forming bars; the microsculpture comprises short spikes. In the soft parts we highlight the few, weak and irregularly distributed lamellar connections of the outer demibranch and some features of the stomach, such as the distally enlarged minor typhlosole. There are records of D. granosus over a large area of South America, from Guiana to Argentina. However, most of these records are related to other species and the distribution of D. granosus is restricted to the north of South America in the basins of the Amazonas and Orinoco rivers, and coastal rivers in between. Despite this wide distribution, the species occurs in specific habitats, mainly streams (igarapés), resulting in an extremely fragmented occurrence. Thus, any disturbance to these habitats can threat this freshwater mussel.

scholarly journals BEST PRACTICE PENGEMBANGAN MUTU SMK TERPADU LAMPANG SUBANG

2019 ◽  
Vol 26 (1) ◽  
pp. 1-16
Author(s):  
Asep Priatna
Keyword(s):  
Best Practice ◽  
Program Planning ◽  
Vocational School ◽  
National Standard ◽  
Content Standards ◽  
Vocational Schools ◽  
Education Standards ◽  
National Education ◽  
The Status ◽  
Long Time

This study aims to reveal the efforts and results that have been achieved by Lampang Subang Integrated Private Vocational Schools in improving the quality of learning to meet national education standards (SNP), so that they become private schools with the status of national standard schools (SSN). This research is a survey research with a quantitative approach. The study was conducted at the Integrated Vocational School of Lampang Subang, West Java. The results showed that the level of achievement of the program that had been compiled in the RPS of Lampang Integrated Vocational School had reached 90% with the main target being the achievement of the UAN level and graduation that had been carried out by teachers both in the preparation of RPPs and teaching materials had reached 85%, Management developed by Integrated Vocational Schools Long-time contributed significant value, especially in program planning and implementation, while the supervision and leadership of the Principal has been running well, so the value obtained is quite significant, while other components that are quite prominent are PBM and content standards that get good enough grades , so that it can be developed further

Sign in / Sign up

Export Citation Format

Share Document