scholarly journals COMPARATIVE VIRULENCE OF ST. LOUIS ENCEPHALITIS VIRUS CULTURED WITH BRAIN TISSUE FROM INNATELY SUSCEPTIBLE AND INNATELY RESISTANT MICE

1941 ◽  
Vol 74 (5) ◽  
pp. 489-494 ◽  
Author(s):  
L. T. Webster ◽  
Mary S. Johnson
Keyword(s):  
Brain Tissue ◽  
High Titre ◽  
Encephalitis Virus ◽  
Similar Solution ◽  
Tyrode Solution ◽  
Culture In Vitro ◽  
The Brain

We find that St. Louis encephalitis virus cultured in 10 per cent serum-Tyrode solution plus brain tissue from 1-day-old innately susceptible mice attains a higher titre than when cultured in a similar solution plus brain tissue from 1-day-old closely related, yet innately resistant mice. This difference in titre persists regardless of whether the serum comes from innately susceptible or resistant mice. The relatively high titre of virus in the susceptible media is not affected by the addition of an extract (not cell-free) from the resistant brain; the relatively low titre of the virus in the resistant media may possibly be slightly enhanced by the addition of an extract from the susceptible brain. The findings as a whole show that the marked difference in the increase of St. Louis encephalitis virus in the brain tissue of innately susceptible and resistant mice, on culture in vitro, is due to some difference in the brain tissue itself.

scholarly journals EXPERIMENTS ON THE SURVIVAL OF THE FEBRILE HERPETIC AND ALLIED VIRUSES IN VITRO

1924 ◽  
Vol 39 (4) ◽  
pp. 533-542 ◽  
Author(s):  
James E. McCartney
Keyword(s):  
Brain Tissue ◽  
Secondary Infection ◽  
The Body ◽  
Herpes Viruses ◽  
Encephalitis Lethargica ◽  
Aerobic Conditions ◽  
Maximum Period ◽  
Suitable Technique ◽  
The Brain

These studies fail to confirm the statements previously made that microorganisms of the class of the globoid bodies of poliomyelitis may be cultivated in the Smith-Noguchi medium from the so called virus of encephalitis lethargica. They show equally that the herpes virus does not multiply in this medium. The experiments indicate, moreover, that the medium is unfavorable to the survival of the virus, while ordinary broth under aerobic conditions is more favorable for maintaining the activity of both the encephalitic and the herpes viruses. Probably no multiplication of either takes place in the latter medium but merely a survival, and for a maximum period of 6 days in the broth itself, and 12 days in the fragment of brain tissue immersed in the broth. Finally, it has been shown that with a suitable technique the viruses can be passed from the brain of one rabbit to that of another through a long series without contamination with cocci or other common bacterial forms. Hence we regard all reports of the finding of ordinary bacteria in the brain of cases of epidemic or lethargic encephalitis as instances of mixed or secondary infection arising during life, or examples of postmortem invasion of the body, or of faulty technique at the autopsy.

scholarly journals Altered expression of DNA damage repair genes in the brain tissue of mice conceived by in vitro fertilization

2020 ◽  
Vol 26 (3) ◽  
pp. 141-153
Author(s):  
Minhao Hu ◽  
Yiyun Lou ◽  
Shuyuan Liu ◽  
Yuchan Mao ◽  
Fang Le ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Brain Tissue ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Gene And Protein Expression ◽  
The Brain ◽  
Repair Genes

Abstract Our previous study revealed a higher incidence of gene dynamic mutation in newborns conceived by IVF, highlighting that IVF may be disruptive to the DNA stability of IVF offspring. However, the underlying mechanisms remain unclear. The DNA damage repair system plays an essential role in gene dynamic mutation and neurodegenerative disease. To evaluate the long-term impact of IVF on DNA damage repair genes, we established an IVF mouse model and analyzed gene and protein expression levels of MSH2, MSH3, MSH6, MLH1, PMS2, OGG1, APEX1, XPA and RPA1 and also the amount of H2AX phosphorylation of serine 139 which is highly suggestive of DNA double-strand break (γH2AX expression level) in the brain tissue of IVF conceived mice and their DNA methylation status using quantitative real-time PCR, western blotting and pyrosequencing. Furthermore, we assessed the capacity of two specific non-physiological factors in IVF procedures during preimplantation development. The results demonstrated that the expression and methylation levels of some DNA damage repair genes in the brain tissue of IVF mice were significantly changed at 3 weeks, 10 weeks and 1.5 years of age, when compared with the in vivo control group. In support of mouse model findings, oxygen concentration of in vitro culture environment was shown to have the capacity to modulate gene expression and DNA methylation levels of some DNA damage repair genes. In summary, our study indicated that IVF could bring about long-term alterations of gene and protein expression and DNA methylation levels of some DNA damage repair genes in the brain tissue and these alterations might be resulted from the different oxygen concentration of culture environment, providing valuable perspectives to improve the safety and efficiency of IVF at early embryonic stage and also throughout different life stages.

scholarly journals THE CHARACTERS OF KUPFFER CELLS LIVING IN VITRO

1934 ◽  
Vol 59 (5) ◽  
pp. 593-607 ◽  
Author(s):  
J. W. Beard ◽  
Peyton Rous
Keyword(s):  
Kupffer Cells ◽  
The Other ◽  
Ground Glass ◽  
Tyrode Solution ◽  
General Aspect ◽  
Blood Leukocytes ◽  
Culture In Vitro ◽  
Other Hand ◽  
Glass Membranes

The Kupffer cells procured from the liver of the rabbit and dog for culture in vitro have the typical characters of clasmatocytes. They are readily discriminated from the monocytes washed from the liver with them; and they have certain peculiar features which suffice to differentiate them from some at least of the clasmatocytes of other organs. Their surface is extraordinarily sticky,—far more so than that of blood leukocytes or of the clasmatocytes found in peritoneal exudates; and in consequence they are exceedingly difficult to handle in vitro. They put forth enormous, pellucid, circular membranes resembling those of exudate clasmatocytes but larger. Splenic clasmatocytes, on the other hand, put forth rather small, one-sided ground-glass membranes like broad tongues. On comparing them with Kupffer cells and exudate clasmatocytes one perceives that they are not wholly identical in their characters, but have secondary peculiarities. However, there exist good morphological reasons for grouping them together and terming them all reticulo-endothelial. Kupffer cells are notably sensitive to injury, surviving in Tyrode solution for a much shorter time than blood leukocytes. However, they can be readily cultured on lens paper in serum. Under such circumstances they scatter on the fibres and live separately, presenting the same general aspect as when in the liver; but in the course of proliferation they soon lose some of their pronounced characters, retaining such as are common to clasmatocytes in general. A considerable population of ordinary leukocytes exists in the hepatic sinuses over and above those circulating in the blood. During infection, their number may greatly increase. Several cubic centimeters of packed white cells have been obtained from the liver of a sick dog. The fact has been realized that leukocytes may stop a while in the liver, yet the extent of the accumulation which sometimes takes place seems deserving of stress.

Studies on the Role of Fibrinolysis and Fibrinogen Degradation Products (FDP) in Analgesic Action of Morphine

1972 ◽  
Vol 28 (03) ◽  
pp. 359-366 ◽  
Author(s):  
Włodzimierz Buczko ◽  
Konstanty Wiśniewski
Keyword(s):  
Molecular Weight ◽  
Brain Tissue ◽  
Clinical Effect ◽  
Degradation Products ◽  
Analgesic Action ◽  
Fibrinogen Degradation Products ◽  
The Brain

SummaryThe role of fibrinolysis and FDP in the analgesic action of morphine in mice and rats was studied. It was shown that during activation of blood fibrinolysis, both the accumulation of morphine in the brain tissue of rats and the clinical effect of this drug were increased. Similar results were observed after morphine given simultaneously with FDP obtained in vitro. The data from the analysis of FDP carried out on Sephadex G-25 Fine columns suggest that only FDP of molecular weight of about 10,000 potentiate the action of morphine; smaller peptides decreased the action of this drug.

Biochemistry

1936 ◽  
Vol 82 (339) ◽  
pp. 431-433
Author(s):  
J. H. Quastel
Keyword(s):  
Nervous System ◽  
Brain Tissue ◽  
Brain Slice ◽  
Brain Slices ◽  
Ringer Solution ◽  
Living Animal ◽  
Dominant Form ◽  
Straight Line ◽  
The Brain

I want to speak of the work we have been doing in Cardiff on the metabolism of the nervous system. The work was carried out there because of the importance of the narcosis treatment. It seemed to us there a pity that a treatment such as that should be given up because of the considerable toxicity possible in relation to it. The research was undertaken to see if we could diminish the toxicity, at the same time seeking an idea as to how narcotics work. I ask that you will realize that the main substance burned by the brain is glucose. The dominant form of metabolism in the nervous system is connected with the breakdown of glucose and lactic acid, and this can be proved by experiment in the living animal and with brain-tissue in vitro. In doing experiments we are not able to carry out work with human brain, because we cannot get human tissue fresh enough, so we have to carry out experiments with animals. They are carried out in this way. We cut slices of the cortex of the brain as soon as the animal is dead, that is to say, within ten minutes of death the brain is out and slices have been cut. They are placed in a physiological medium in the presence of glucose, and we follow the metabolism of that tissue, which allows us to estimate the amount of oxygen being taken up by the brain. If luminal, chloretone, hyoscine or somnifaine be placed with the brain-tissue, then the respiration, instead of being at the usual level, starts lower down, and maintains a straight line. We wanted to see whether this action is reversible or irreversible. If the latter, then on removing the brain-slices from the narcotic it should no longer behave like a normal piece of tissue. Actually, when the brain-slice is removed and placed in Ringer solution, with no narcotic, the respiration goes up and becomes equal to that shown by the slice which had no narcotic. That is to say, the process is reversible.

scholarly journals Efavirenz Is Predicted To Accumulate in Brain Tissue: an In Silico, In Vitro, and In Vivo Investigation

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Paul Curley ◽  
Rajith K. R. Rajoli ◽  
Darren M. Moss ◽  
Neill J. Liptrott ◽  
Scott Letendre ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Drug Distribution ◽  
Pbpk Modeling ◽  
Once Daily ◽  
Plasma Ratio ◽  
Human Data ◽  
High Concentrations ◽  
The Brain

ABSTRACT Adequate concentrations of efavirenz in the central nervous system (CNS) are necessary to suppress viral replication, but high concentrations may increase the likelihood of CNS adverse drug reactions. The aim of this investigation was to evaluate the efavirenz distribution in the cerebrospinal fluid (CSF) and the brain by using a physiologically based pharmacokinetic (PBPK) simulation for comparison with rodent and human data. The efavirenz CNS distribution was calculated using a permeability-limited model on a virtual cohort of 100 patients receiving efavirenz (600 mg once daily). Simulation data were then compared with human data from the literature and with rodent data. Wistar rats were administered efavirenz (10 mg kg of body weight−1) once daily over 5 weeks. Plasma and brain tissue were collected for analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The median maximum concentrations of drug (C max) were predicted to be 3,184 ng ml−1 (interquartile range [IQR], 2,219 to 4,851 ng ml−1), 49.9 ng ml−1 (IQR, 36.6 to 69.7 ng ml−1), and 50,343 ng ml−1 (IQR, 38,351 to 65,799 ng ml−1) in plasma, CSF, and brain tissue, respectively, giving a tissue-to-plasma ratio of 15.8. Following 5 weeks of oral dosing of efavirenz (10 mg kg−1), the median plasma and brain tissue concentrations in rats were 69.7 ng ml−1 (IQR, 44.9 to 130.6 ng ml−1) and 702.9 ng ml−1 (IQR, 475.5 to 1,018.0 ng ml−1), respectively, and the median tissue-to-plasma ratio was 9.5 (IQR, 7.0 to 10.9). Although it is useful, measurement of CSF concentrations may give an underestimation of the penetration of antiretrovirals into the brain. The limitations associated with obtaining tissue biopsy specimens and paired plasma and CSF samples from patients make PBPK modeling an attractive tool for probing drug distribution.

scholarly journals Complexing amphotericin B with gold nanoparticles improves fungal clearance from the brains of mice infected with Cryptococcal neoformans

2021 ◽  
Author(s):  
Koteswara R Chintalacharuvu ◽  
Zlatko A Matolek ◽  
Benny Pacheco ◽  
Erick M Carriera ◽  
David O Beenhouwer
Keyword(s):  
Gold Nanoparticles ◽  
Brain Tissue ◽  
Amphotericin B ◽  
Human Red Blood Cells ◽  
Β Phase ◽  
Α Phase ◽  
Plasma Half Life ◽  
Higher Doses ◽  
The Brain

Abstract Amphotericin B (AmB) is used to treat cryptococcal meningoencephalitis. However, the mortality rate remains high. Higher doses of AmB in deoxycholate buffer (AmBd) are toxic to human red blood cells (hRBC) and have no effect on brain organism load in mice. Here we show that while AmBd lysed 96% of hRBC, AmB complexed with gold nanoparticles (AuNP-SA-AmB) lysed only 27% of hRBC. In vitro growth of C. neoformans was inhibited by 0.25 μg/ml AmBd and 0.04 μg/ml of AuNP-SA-AmB. In mice infected with C. neoformans, five daily treatments with AuNP-SA-AmB containing 0.25 mg/kg AmB significantly lowered the fungal burden in the brain tissue compared to either untreated or treatment with 0.25 mg/kg of AmBd. When a single dose of AmBd was injected intravenously into BALB/c mice, 81.61% of AmB cleared in the α-phase and 18.39% cleared in the β-phase at a rate of 0.34% per hour. In contrast, when AuNP-SA-AmB was injected, 49.19% of AmB cleared in the α-phase and 50.81% of AmB cleared in the β-phase at a rate of 0.27% per hour. These results suggest that AmB complexed with gold nanoparticles is less toxic to hRBC, is more effective against C. neoformans and persists longer in blood when injected into mice resulting in more effective clearing of C. neoformans from the brain tissue. Lay summary Amphotericin B (AmB) was complexed with gold nanoparticles (AuNP-SA-AmB) to improve brain delivery. AuNP-SA-AmB was more effective than AmB alone in clearing of Cryptococcus neoformans from the brain tissue of infected mice. This may be due to longer plasma half-life of AmB as AuNP-SA-AmB.

scholarly journals Electroencephalographic Recovery, Hypnotic Emergence, and the Effects of Metabolite after Continuous Infusions of a Rapidly Metabolized Etomidate Analog in Rats

2012 ◽  
Vol 116 (5) ◽  
pp. 1057-1065 ◽  
Author(s):  
Ervin Pejo ◽  
Rile Ge ◽  
Natalie Banacos ◽  
Joseph F. Cotten ◽  
S. Shaukat Husain ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Half Life ◽  
Suppression Ratio ◽  
Burst Suppression ◽  
Closed Loop System ◽  
Pharmacologic Effect ◽  
Pharmacologically Active ◽  
The Brain ◽  
Infusion Duration

Background Methoxycarbonyl etomidate is an ultrarapidly metabolized etomidate analog. It is metabolized to methoxycarbonyl etomidate carboxylic acid (MOC-ECA), which has a hypnotic potency that is 350-fold less than that of methoxycarbonyl etomidate. The authors explored the relationships between methoxycarbonyl etomidate infusion duration, recovery time, metabolite concentrations in blood and cerebrospinal fluid (CSF), and methoxycarbonyl etomidate metabolism in brain tissue and CSF to test the hypothesis that rapid metabolism of methoxycarbonyl etomidate may lead to sufficient accumulation of MOC-ECA in the brain to produce a pharmacologic effect. Methods A closed-loop system with burst suppression ratio feedback was used to administer methoxycarbonyl etomidate infusions of varying durations to rats. After infusion, recovery of the electroencephalogram and righting reflexes were assessed. MOC-ECA concentrations were measured in blood and CSF during and after methoxycarbonyl etomidate infusion, and the in vitro half-life of methoxycarbonyl etomidate was determined in rat brain tissue and CSF. Results Upon termination of continuous methoxycarbonyl etomidate infusions, the burst suppression ratio recovered in a biexponential manner with fast and slow components having time constants that differed by more than 100-fold and amplitudes that varied inversely with infusion duration. MOC-ECA concentrations reached hypnotic concentrations in the CSF with prolonged methoxycarbonyl etomidate infusion and then decreased during a period of several hours after infusion termination. The metabolic half-life of methoxycarbonyl etomidate in brain tissue and CSF was 11 and 20 min, respectively. Conclusion In rats, methoxycarbonyl etomidate metabolism is sufficiently fast to produce pharmacologically active MOC-ECA concentrations in the brain with prolonged methoxycarbonyl etomidate infusion.

Intracerebral Chemotherapy

Neurosurgery ◽  
1982 ◽  
Vol 10 (3) ◽  
pp. 349-354 ◽  
Author(s):  
Jeffrey S. Kroin ◽  
Richard D. Penn
Keyword(s):  
Brain Tissue ◽  
Brain Neoplasms ◽  
Animal Studies ◽  
The Body ◽  
Therapeutic Drug ◽  
Systemic Injection ◽  
Drug Levels ◽  
Hydrophilic Drugs ◽  
The Brain

Abstract Cisplatin, a chemotherapeutic agent used to treat tumors in many parts of the body, does not reach brain tissue during systemic injection because of the blood-brain barrier and protein binding in the blood. To allow hydrophilic drugs, such as cisplatin, to reach brain neoplasms with minimal body toxicity, we tested chronic intracerebral microperfusion into the extracellular space of the brain in normal rats. Small stainless steel cannulas connected to osmotic minipumps were stereotactically placed in the midline cerebellum or frontal cortex, and cisplatin was pumped into the brain at the rate of 0.9 μg/hour for periods of up to 7 days. Brain tissue was then analyzed for the total platinum content, at 1-mm intervals from the cannula tip, using atomic absorption spectroscopy. The results of the animal studies show that a platinum concentration of 2 ng/mg of tissue, wet weight, can be maintained over a 1-cm region of brain. If all of the extracellular platinum has remained in the active cisplatin form, then this would be equivalent to a drug concentration of 10 μM. Cisplatin at this constant level has been shown to have a therapeutic effect against various tumor lines in vitro. To extend these results to human brain neoplasms, we estimate that one cannula would be sufficient to treat a 1-cm tumor or a larger tumor that could be surgically reduced. For inoperable tumors of up to 2 cm in diameter, a multiple cannula system would be required to yield the 10 μM concentration throughout. For larger inoperable tumors, local infusion will not produce high enough drug levels. In conclusion, chronic intracerebral microinfusion can be used to produce adequate and sustained therapeutic drug levels over a considerable region of tissue without the problem of systemic toxicity.

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