Experimental meningococcal infection in neonatal mice: differences in virulence between strains isolated from human cases and carriers

1984 ◽  
Vol 30 (8) ◽  
pp. 1042-1045 ◽  
Author(s):  
Irving E. Salit ◽  
Lewis Tomalty

The lack of availability of a suitable animal model has limited understanding of the pathophysiology of meningococcal disease. We have utilized a neonatal mouse model in which atraumatic intranasal inoculation of meningococci results in nasopharyngeal colonization and ultimately bacteremia. Using this model, we compared the virulence of seven encapsulated meningococcal carrier strains with eight meningococcal strains which were isolated from cerebrospinal fluid or blood of patients (disease strains). Intraperitoneal (IP) iron dextran was given to some animals to enhance meningococcal virulence. After IP iron, carrier strains were still poorly invasive with rates of bacteremia ranging from 0 to 15% (mean = 3%), whereas disease-associated strains were significantly more invasive and caused bacteremia in 31–64% of animals (mean = 39%). Without iron injections, nasopharyngeal colonization rates were similar (36 versus 30%, P > 0.1) for case and carrier strains IP iron dextran significantly enhanced rates of colonization and bacteremia caused by the disease strains only. We have therefore, shown that the relative virulence of meningococcal strains for humans is maintained in this experimental model.

1984 ◽  
Vol 30 (8) ◽  
pp. 1022-1029 ◽  
Author(s):  
Irving E. Salit ◽  
Elaine Van Melle ◽  
Lewis Tomalty

A more complete understanding of meningococcal disease has been hampered by lack of an appropriate animal model. We subjected 5-day-old guinea pigs, rats, and mice to intranasal challenge with meningococci and we measured rates of bacteremia as a marker of mucosal invasion. After a single intranasal instillation of 107 serotype 2 meningococci, positive blood cultures were found in 0% of guinea pigs, 16% of rats, and 39% of mice, and so mice were used for further studies. Death occurred in 4% of mice and was associated with a purulent leptomeningitis and ventriculitis. Forty percent of mice had nasopharyngeal colonization which increased to 65% with repeated injections. Carrier strains were avirulent, a nonserotype 2 disease strain had low invasiveness, and serotype 2 strains were most virulent. Iron dextran increased rates of bacteremia after challenge with serotype 2 strains. Adult animals were not susceptible to bacteremia after intranasal challenge. The neonatal mouse model fulfills most of the criteria for an appropriate experimental model of meningococcal disease.


Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.


2020 ◽  
Vol 19 (2) ◽  
pp. 56-62
Author(s):  
M. I. Gritsay ◽  
M. A. Koroleva ◽  
N. N. Fomkina ◽  
I. S. Koroleva

Aims. The purpose of this study was to identify current epidemiological features of meningococcal infection in Moscow.Materials and methods. Cases of invasive meningococcal disease in Moscow from 2014 to 2018 and the biomaterial from patients with an invasive meningococcal disease were analyzed.Results. The features of the epidemic process of meningococcal disease in Moscow were revealed: increasing in the incidence rate involving teenagers and young adults into the epidemic process; meningococcal strains of serogroups W and A increased in the etiology of the invasive meningococcal disease; high mortality rate.Conclusions. It seems reasonable to recommend vaccination against meningococcal disease by including adolescents, young adults and persons over 65 years old.


2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Katherine M Ranard ◽  
Matthew J Kuchan ◽  
John W Erdman

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.


1991 ◽  
Vol 69 (9) ◽  
pp. 1381-1384 ◽  
Author(s):  
Knud Poulsen ◽  
Arne Høj Nielsen ◽  
Arne Johannessen

In a new method for measurement of inactive rat plasma renin, the trypsin generated angiotensin I immunoreactive material, which was HPLC characterized as similar to tetradecapeptide renin substrate, is removed by a cation exchange resin before the renin incubation step. The method also corrects for trypsin destruction of endogenous angiotensinogen by the addition of exogenous angiotensinogen. When measured with this method inactive renin in rat plasma decreased after nephrectomy and increased after adrenalectomy. This is in accordance with findings in humans. A sexual dimorphism of prorenin (inactive renin) in rat plasma, similar to that reported in humans and mice, was demonstrated. Thus, inactive renin in the rat is no exception among species, and the rat might be a suitable animal model for further studies dealing with the physiology of prorenin in plasma and tissues.Key words: angiotensinogen, inactive renin, renin.


2010 ◽  
Vol 84 (21) ◽  
pp. 11089-11100 ◽  
Author(s):  
Dennis A. Bente ◽  
Judie B. Alimonti ◽  
Wun-Ju Shieh ◽  
Gaëlle Camus ◽  
Ute Ströher ◽  
...  

ABSTRACT Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic syndrome in humans but not in its vertebrate animal hosts. The pathogenesis of the disease is largely not understood due to the lack of an animal model. Laboratory animals typically show no overt signs of disease. Here, we describe a new small-animal model to study CCHFV pathogenesis that manifests clinical disease, similar to that seen in humans, without adaptation of the virus to the host. Our studies revealed that mice deficient in the STAT-1 signaling molecule were highly susceptible to infection, succumbing within 3 to 5 days. After CCHFV challenge, mice exhibited fever, leukopenia, thrombocytopenia, and highly elevated liver enzymes. Rapid viremic dissemination and extensive replication in visceral organs, mainly in liver and spleen, were associated with prominent histopathologic changes in these organs. Dramatically elevated proinflammatory cytokine levels were detected in the blood of the animals, suggestive of a cytokine storm. Immunologic analysis revealed delayed immune cell activation and intensive lymphocyte depletion. Furthermore, this study also demonstrated that ribavirin, a suggested treatment in human cases, protects mice from lethal CCHFV challenge. In conclusion, our data demonstrate that the interferon response is crucial in controlling CCHFV replication in this model, and this is the first study that offers an in-depth in vivo analysis of CCHFV pathophysiology. This new mouse model exhibits key features of fatal human CCHF, proves useful for the testing of therapeutic strategies, and can be used to study virus attenuation.


2002 ◽  
Vol 114 (2) ◽  
pp. 181-183 ◽  
Author(s):  
Alexander Zeidel ◽  
Moshe M Melloul ◽  
Eduard Maiburd ◽  
Dov Dicker ◽  
Benzion Beilin

2013 ◽  
Vol 71 (10) ◽  
pp. 802-806 ◽  
Author(s):  
Almir Ferreira de Andrade ◽  
Matheus Schmidt Soares ◽  
Gustavo Cartaxo Patriota ◽  
Alessandro Rodrigo Belon ◽  
Wellingson Silva Paiva ◽  
...  

Objective Intracranial hypertension (IH) develops in approximately 50% of all patients with severe traumatic brain injury (TBI). Therefore, it is very important to identify a suitable animal model to study and understand the pathophysiology of refractory IH to develop effective treatments. Methods We describe a new experimental porcine model designed to simulate expansive brain hematoma causing IH. Under anesthesia, IH was simulated with a balloon insufflation. The IH variables were measured with intracranial pressure (ICP) parenchymal monitoring, epidural, cerebral oximetry, and transcranial Doppler (TCD). Results None of the animals died during the experiment. The ICP epidural showed a slower rise compared with parenchymal ICP. We found a correlation between ICP and cerebral oximetry. Conclusion The model described here seems useful to understand some of the pathophysiological characteristics of acute IH.


2016 ◽  
Vol 15 (3) ◽  
pp. 7-14 ◽  
Author(s):  
M. A. Koroleva ◽  
I. S. Koroleva ◽  
I. M. Zakroeva ◽  
I. M. Gruber

Relevance. One of the prognostic criteria meningococcal infection (MI) epidemic status process is the increasing number of resistant to antibiotics meningococcal strains. Aim of this study was to investigate the dynamics of invasive strains of N. meningitidis susceptibility to antibiotics in Moscow in 2006 - 2015. Materials and methods. Studied 98 strains of N. meningitidis, isolated from blood and cerebrospinal fluid of patients with MI. The study changes of sensitivity N. meningitidis to antibiotics was occured in two periods: first -2006 - 2011 and second - 2012 - 2015. The MIC was determined by E-test. Results. In the present study revealed for the first time the Russian strains of N. meningitidis, moderately resistant to penicillin (5 strains) and resistant to rifampicin (3 strains). Among the studied strains were not found resistant to ceftriaxone, ciprofloxacin, tetracycline and chloramphenicol. Discussion. Comparison results two study periods allowed to reveal the dynamics of increasing the sensitivity of N. meningitidis to antibiotics, which confirms the decline in meningococcal virulence, and as a result, continued interepidemic MI period. Conclusions. Despite the decline antibakterial resistance is required continuous monitoring.


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