scholarly journals Studies on the Novel Antiallergic Agent HSR-609: Its Penetration into the Central Nervous System in Mice and Guinea Pigs and Its Selectivity for the Histamine H1Receptor

1997 ◽  
Vol 73 (4) ◽  
pp. 291-298 ◽  
Author(s):  
Masato Kakiuchi ◽  
Tetsuo Ohashi ◽  
Keiichi Musoh ◽  
Kimio Kawamura ◽  
Kouji Morikawa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Guinea Pigs ◽  
The Novel ◽  
The Central Nervous System ◽  
Antiallergic Agent

scholarly journals COVID-19 Vaccination: From Interesting Agent to the Patient

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 120
Author(s):  
Anis Daou
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gastrointestinal Tract ◽  
Circulatory System ◽  
The Novel ◽  
Lead Compound ◽  
Fda Approval ◽  
The World ◽  
The Central Nervous System ◽  
Novel Coronavirus

The vaccination for the novel Coronavirus (COVID-19) is undergoing its final stages of analysis and testing. It is an impressive feat under the circumstances that we are on the verge of a potential breakthrough vaccination. This will help reduce the stress for millions of people around the globe, helping to restore worldwide normalcy. In this review, the analysis looks into how the new branch of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) came into the forefront of the world like a pandemic. This review will break down the details of what COVID-19 is, the viral family it belongs to and its background of how this family of viruses alters bodily functions by attacking vital human respiratory organs, the circulatory system, the central nervous system and the gastrointestinal tract. This review also looks at the process a new drug analogue undergoes, from (i) being a promising lead compound to (ii) being released into the market, from the drug development and discovery stage right through to FDA approval and aftermarket research. This review also addresses viable reasoning as to why the SARS-CoV-2 vaccine may have taken much less time than normal in order for it to be released for use.

scholarly journals A novel gene signature based on five immune checkpoint genes predicts the survival of glioma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Wei Zhang ◽  
You Zhai ◽  
Guanzhang Li ◽  
Tao Jiang
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Cox Regression ◽  
Gene Signature ◽  
Immune Checkpoints ◽  
The Novel ◽  
The Central Nervous System ◽  
Checkpoint Genes

Abstract Background Glioma is the most common and fatal type of nerve neoplasm in the central nervous system. Several biomarkers have been considered for prognosis prediction, which is not accurate enough. We aimed to carry out a gene signature related to the expression of immune checkpoints which was enough for its performance in prediction. Methods Gene expression of immune checkpoints in TGGA database was filtrated. The 5 selected genes underwent verification by COX and Lasso-COX regression. Next, the selected genes were included to build a novel signature for further analysis. Results Patients were sub-grouped into high and low risk according to the novel signature. Immune response, clinicopathologic characters, and survival showed significant differences between those 2 groups. Terms including “naive,” “effector,” and “IL-4” were screened out by GSEA. The results showed strong relevance between the signature and immune response. Conclusions We constructed a gene signature with 5 immune checkpoints. The signature predicted survival effectively. The novel signature performed more functional than previous biomarkers.

scholarly journals A PARALYTIC DISEASE OF GUINEA PIGS DUE TO THE TUBERCLE BACILLUS

1929 ◽  
Vol 50 (3) ◽  
pp. 365-370 ◽  
Author(s):  
Richard E. Shope ◽  
Paul A. Lewis
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tuberculous Meningitis ◽  
Guinea Pigs ◽  
Tuberculous Infection ◽  
Tubercle Bacillus ◽  
Herpes Encephalitis ◽  
Subsequent Publication ◽  
The Central Nervous System ◽  
Rule Out

The experimental data collected during this study of a transmissible type of paralysis developing in tuberculous guinea pigs indicate the condition to be a true tuberculous meningitis. We have been able to rule out the possibility that it is due to a non-tuberculous infection of the central nervous system caused by Roemer's virus, or by an atypical herpes virus, or by some bacterium other than the tubercle bacillus. Roemer's virus and herpes could be eliminated from consideration when Berkefeld N filtrates of infectious brain emulsions proved incapable of reproducing the disease. Furthermore, rabbits could be infected as they cannot with Roemer's virus, and the disease elicited in rabbits bears no semblance to herpes encephalitis. No organism other than the tubercle bacillus could be obtained on culturing brain or brain emulsions from experimental cases, and no others were seen in examining fresh smear preparations from the central nervous system. In a modified Noguchi medium a tubercle bacillus possessing atypical staining properties was obtained. This organism was capable of producing the typical paralytic disease when injected intracerebrally into guinea pigs, and also generalized tuberculosis in animals inoculated subcutaneously with it. Typical tuberde bacilli were readily demonstrable in sections of the meninges from animals with the disease, and culture of pieces of brain on Dorset's egg medium usually yielded a growth of tubercle bacilli. Only in the first of the experimental passages, on the other hand, was it possible to demonstrate acid-fast organisms in fresh smear preparations from the central nervous system. This fact and the attributes of the atypically staining organisms encountered in the cultures in Noguchi media will be considered more fully in a subsequent publication. In view of the much discussed question of the filtrability of the tubercle bacillus our observations concerning the failure of this organism to pass a Berkefeld N filter are of interest. No animal in our series inoculated intracerebrally with brain emulsion from either a "spontaneous" or experimental case of tuberculous meningitis failed to develop meningitis, and that rather acutely, while no animal in our series injected with a Berkefeld filtrate of brain emulsion has developed tuberculous meningitis or any other form of tuberculosis. In connection with this observation it must be recalled that the organism was atypical in respect to its staining qualities at least.

scholarly journals Characterization of More Selective Central Nervous System Nrf2-Activating Novel Vinyl Sulfoximine Compounds Compared to Dimethyl Fumarate

2020 ◽  
Vol 17 (3) ◽  
pp. 1142-1152 ◽  
Author(s):  
Karl E. Carlström ◽  
Praveen K. Chinthakindi ◽  
Belén Espinosa ◽  
Faiez Al Nimer ◽  
Elias S. J. Arnér ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
De Novo ◽  
Dimethyl Fumarate ◽  
The Novel ◽  
The Central Nervous System ◽  
Demyelinating Disorders ◽  
Target Effects

Abstract The Nrf2 transcription factor is a key regulator of redox reactions and considered the main target for the multiple sclerosis (MS) drug dimethyl fumarate (DMF). However, exploration of additional Nrf2-activating compounds is motivated, since DMF displays significant off-target effects and has a relatively poor penetrance to the central nervous system (CNS). We de novo synthesized eight vinyl sulfone and sulfoximine compounds (CH-1–CH-8) and evaluated their capacity to activate the transcription factors Nrf2, NFκB, and HIF1 in comparison with DMF using the pTRAF platform. The novel sulfoximine CH-3 was the most promising candidate and selected for further comparison in vivo and later an experimental model for traumatic brain injury (TBI). CH-3 and DMF displayed comparable capacity to activate Nrf2 and downstream transcripts in vitro, but with less off-target effects on HIF1 from CH-3. This was verified in cultured microglia and oligodendrocytes (OLs) and subsequently in vivo in rats. Following TBI, DMF lowered the number of leukocytes in blood and also decreased axonal degeneration. CH-3 preserved or increased the number of pre-myelinating OL. While both CH-3 and DMF activated Nrf2, CH-3 showed less off-target effects and displayed more selective OL associated effects. Further studies with Nrf2-acting compounds are promising candidates to explore potential myelin protective or regenerative effects in demyelinating disorders.

Central nervous system control of airway tone in guinea pigs: the role of histamine

1988 ◽  
Vol 65 (5) ◽  
pp. 2024-2029 ◽  
Author(s):  
P. J. Mauser ◽  
N. H. Edelman ◽  
R. W. Chapman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Guinea Pigs ◽  
Lung Compliance ◽  
System Control ◽  
The Central Nervous System ◽  
Dose Dependent Decrease ◽  
Airway Tone ◽  
Dynamic Lung Compliance ◽  
H1 Antagonist

The central nervous system (CNS) plays an important role in the reflex control of bronchomotor tone, but the relevant neurotransmitters and neuromodulators have not been identified. In this study we have investigated the effect of histamine. Anesthetized male guinea pigs were prepared with a chronically implanted intracerebroventricular (icv) cannula and instrumented for the measurement of pulmonary resistance (RL), dynamic lung compliance (Cdyn), tidal volume (VT), respiratory rate (f), blood pressure (BP), and heart rate (HR). Administration of histamine (2-30 micrograms) icv caused a significant (P less than 0.05) reduction of Cdyn with no change in RL, VT, and f. At a dose of 100 micrograms icv, histamine caused an increase in RL (202 +/- 78%), a reduction of Cdyn (77 +/- 9%), an increase in f (181 +/- 64%), and a reduction of VT (53 +/- 18%). There were no changes in BP and HR after 100 micrograms of icv histamine. In contrast, intravenous administration of histamine (0.1-2 micrograms/kg) caused a dose-dependent decrease in Cdyn and increase in RL that was associated with tachypnea at each bronchoconstrictor dose. Intravenous histamine (2 micrograms/kg) produced a fall in BP and an increase in HR. The bronchoconstrictor responses to icv histamine were completely blocked by vagotomy and significantly reduced by atropine (0.1 mg/kg iv), whereas vagotomy and atropine did not block the bronchospasm due to intravenous histamine. Additional studies indicated that the pulmonary responses due to icv histamine (100 micrograms) were blocked by pretreatment with the H1-antagonist chlorpheniramine (1 and 10 micrograms, icv). These data indicate that histamine may serve a CNS neurotransmitter function in reflex bronchoconstriction in guinea pigs.

scholarly journals INDUCED RESISTANCE OF THE CENTRAL NERVOUS SYSTEM TO EXPERIMENTAL INFECTION WITH EQUINE ENCEPHALOMYELITIS VIRUS

1944 ◽  
Vol 80 (3) ◽  
pp. 197-211 ◽  
Author(s):  
R. Walter Schlesinger ◽  
Peter K. Olitsky ◽  
Isabel M. Morgan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Guinea Pigs ◽  
Early Stage ◽  
Neutralizing Antibody ◽  
Challenge Dose ◽  
Abortive Infection ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System ◽  
Western Equine Encephalomyelitis Virus

Although vaccination of guinea pigs with formalin-inactivated Western equine encephalomyelitis virus rendered them specifically immune to an intracerebral challenge dose of 1,000 M.L.D. of Western virus, it failed to protect their central nervous system against the initial effects of the virus: the intracerebral challenge dose was followed by an abortive infection of 20 to 30 hours' duration characterized by fever and histopathological changes which simulated the response at that early stage of non-vaccinated control animals. During the abortive infection of immune animals, virus could occasionally be demonstrated in their brains; indeed, it was detected with about the same frequency it was isolated from brains of similarly inoculated, non-immune guinea pigs during corresponding early phases of the infection. About one week after the abortive infection there was found a marked transitory accumulation of specific neutralizing antibody in the brain tissue. See PDF for Equation equalled at this time 1:1 to 1:10 instead of the value of about 1:300 found under physiological conditions. Guinea pigs which had recovered from an abortive infection with Western virus were resistant for a limited period of time to the effects of intracerebral inoculations of the immunologically distinct viruses of Eastern equine encephalomyelitis or vesicular stomatitis.

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