scholarly journals Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878

2020 ◽  
Author(s):  
Bhagwati Khatri ◽  
James Keeble ◽  
Belinda Dagg ◽  
Daryan A. Kaveh ◽  
Philip J. Hogarth ◽  
...  

AbstractIn this study, 2 strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette-Guérin (BCG) Danish doses from 3×105 to 30 CFU/mouse, followed by either immunogenicity evaluation or aerosol infection with Mycobacterium tuberculosis (a laboratory strain H37Rv or West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant protection in their lungs with BCG doses at 3×105 – 3000 CFU (BALB/c) and 3×105-300 CFU (CB6F1). Whereas, both strains of mice when infected with H37Rv, significant protection was seen in BCG doses at 3×105 - 300 CFU. Immunological evaluation revealed interesting results; i) both strains of mice demonstrated a significant increase in the frequencies of BCG-specific IFNγ+ IL2+ TNFα+ CD4 T cells in the BCG doses at 3×105 – 3000 CFU (BALB/c) and 3×105 - 300 CFU (CB6F1); ii) secretion of IL2 and IFNγ were correlated with the bacterial burden in the lungs of HN878 infected CB6F1 mice. The study demonstrated a BCG dose at 3000 CFU (an equivalent single human dose in the mice by body weight index) is protective in both strains of mice and the use of a virulent clinical isolate in testing new tuberculosis vaccine/advancing research is recommended.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bhagwati Khatri ◽  
James Keeble ◽  
Belinda Dagg ◽  
Daryan A. Kaveh ◽  
Philip J. Hogarth ◽  
...  

AbstractTwo strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette-Guérin (BCG) Danish doses from 3 × 105 to 30 CFU/mouse, followed by aerosol infection with Mtb (H37Rv or West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant protection in their lungs with BCG doses at 3 × 105—3000 CFU (BALB/c) and 3 × 105—300 CFU (CB6F1). Whereas, a significant protection was seen in both strains of mice with BCG doses at 3 × 105—300 CFU when infected with H37Rv. A significant increase in the frequencies of BCG-specific IFNγ+ IL2+ TNFα+ CD4 T cells in the BCG doses at 3 × 105—3000 CFU (BALB/c) and 3 × 105—300 CFU (CB6F1) was seen. The IFNγ+ IL2+ TNFα+ CD4 T cells correlated with the Mtb burden in the lungs of HN878 infected mice (BALB/c and CB6F1) whereas, IFNγ+ TNFα+ CD4 T cells correlated with the BALB/c mice infected with H37Rv or HN878. The BCG dose at 3000 CFU (an equivalent single human dose in the mice by body weight) is protective in both strains of mice infected with H37Rv or HN878 and may serve an interesting dose to test new TB vaccine in a preclinical animal model.


2021 ◽  
pp. 109158182098607
Author(s):  
Narendra S. Deshmukh ◽  
Shailesh Gumaste ◽  
Silma Subah ◽  
Nathasha Omal Bogoda

Palmitoylethanolamide (PEA) is an endogenous ethanolamine playing a protective and homeodynamic role in animals and plants. Prenatal developmental toxicity of PEA was tested following oral administration to pregnant female Wistar rats, from days 0 to 19 of gestation, at dosage of 250, 500, or 1,000 mg/kg body weight, according to Organisation for Economic Co-operation and Development Test Guideline No. 414. On gestation day 20, cesarean sections were performed on the dams, followed by examination of their ovaries and uterine contents. The fetuses were further examined for external, visceral, and skeletal abnormalities. Palmitoylethanolamide did not cause any alterations at any of the given dosages in the measured maternal parameters of systemic toxicity (body weight, food consumption, survival, thyroid functions, organ weight, histopathology), reproductive toxicity (preimplantation and postimplantation losses, uterus weight, number of live/dead implants and early/late resorptions, litter size and weights, number of fetuses, their sex ratio), and fetal external, visceral, or skeletal observations. Any alterations that were recorded were “normal variations” or “minor anomalies,” which were unrelated to treatment with PEA. Under the condition of this prenatal study, the no-observed-adverse-effect level of PEA for maternal toxicity, embryotoxicity, fetotoxicity, and teratogenicity in rats was found to be >1,000 mg/kg body weight/d. It indicates that PEA is well tolerated by and is safe to pregnant rats even at a high dose of 1,000 mg/kg body weight/d, equivalent to a human dose of greater than 9.7 g/d. This prenatal developmental toxicity study contributes greatly in building a robust safety profile for PEA.


2010 ◽  
Vol 29 (3) ◽  
pp. 313-317
Author(s):  
Waleed A. Al-Madani ◽  
Nikhat J. Siddiqi ◽  
Abdullah S. Alhomida ◽  
Haseeb A. Khan ◽  
Ibrahim A. Arif ◽  
...  

This investigation was aimed to study the effect of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on mercuric chloride (HgCl2)-induced alterations in urinary excretion of various carnitine fractions including free carnitine (FC), acylcarnitine (AC), and total carnitine (TC). Different groups of Wistar male rats were treated with HgCl2 at the doses of 0.1, 0.5, 1.0, 2.0, and 3.0 mg/kg body weight, and the animals were sacrificed at 24 hours following HgCl2 injection. A separate batch of animals received HgCl2 (2 mg/kg) with or without DMPS (100 mg/kg) and sacrificed at 24 or 48 hours after dosing. Administration of HgCl2 resulted in statistically significant and dose-dependent increase in the urinary excretion of FC, AC, and TC in rats. However, the ratio of urinary AC:FC was significantly decreased by HgCl2. Pretreatment with DMPS offered statistically significant protection against HgCl2-induced alterations in various urinary carnitine fractions in rats.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3069 ◽  
Author(s):  
Anastasia Khandazhinskaya ◽  
Liudmila Alexandrova ◽  
Elena Matyugina ◽  
Pavel Solyev ◽  
Olga Efremenkova ◽  
...  

A series of novel 5′-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of Mycobacterium smegmatis was completely inhibited by the most active compounds at a MIC99 of 67 μg/mL (mc2155) and a MIC99 of 6.7–67 μg/mL (VKPM Ac 1339). Several compounds also showed the ability to inhibit the growth of attenuated strains of Mycobacterium tuberculosis ATCC 25177 (MIC99 28–61 μg/mL) and Mycobacterium bovis ATCC 35737 (MIC99 50–60 μg/mL), as well as two virulent strains of M. tuberculosis; a laboratory strain H37Rv (MIC99 20–50 μg/mL) and a clinical strain with multiple drug resistance MS-115 (MIC99 20–50 μg/mL). Transmission electron microscopy (TEM) evaluation of M. tuberculosis H37Rv bacterial cells treated with one of the compounds demonstrated destruction of the bacterial cell wall, suggesting that the mechanism of action for these compounds may be related to their interactions with bacteria cell walls.


2005 ◽  
Vol 93 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Hui-Ting Yang ◽  
Shyh-Hsiang Lin ◽  
Shih-Yi Huang ◽  
Hsin-Ju Chou

In this study, we attempted to evaluate the effect of administration of a high quantity of red yeast rice on coenzyme Q10 (CoQ10) synthesis in the tissues of ICR mice. Eighty-eight adult male ICR mice were housed and divided into control and experimental groups for red yeast rice treatment. Animals were gavaged with a low (1 g/kg body weight) or a high dose (5 g/kg body weight, approximately five times the typical recommended human dose) of red yeast rice dissolved in soyabean oil. After gavagement, animals of the control group were immediately killed; mice of the experimental groups (eight for each subgroup) were killed at different time intervals of 0·5, 1, 1·5, 4 and 24 h. The liver, heart and kidney were taken for analysis of monacolin K (liver only) and CoQ10 analysis. Liver and heart CoQ10 levels declined dramatically in both groups administered red yeast rice, especially in the high-dose group, within 30 min. After 24 h, the levels of hepatic and cardiac CoQ10 were still reduced. A similar trend was also observed in the heart, but the inhibitory effect began after 90 min. The higher dose of red yeast rice presented a greater suppressive effect than did the lower dose on tissue CoQ10 levels. In conclusion, acute red yeast rice gavage suppressed hepatic and cardiac CoQ10 levels in rodents; furthermore, the inhibitory effect was responsive to the doses administered.


2016 ◽  
Vol 48 (2) ◽  
pp. 578-582 ◽  
Author(s):  
L. García-Covarrubias ◽  
C. Pliego ◽  
L. Bermudez ◽  
A. Cicero ◽  
J. Cancino ◽  
...  

2000 ◽  
Vol 44 (12) ◽  
pp. 3298-3301 ◽  
Author(s):  
Glenn P. Morlock ◽  
Bonnie B. Plikaytis ◽  
Jack T. Crawford

ABSTRACT Resistance to rifampin in Mycobacterium tuberculosisresults from mutations in the gene coding for the beta subunit of RNA polymerase (rpoB). At least 95% of rifampin-resistant isolates have mutations in rpoB, and the mutations are clustered in a small region. About 40 distinct point mutations and in-frame insertions and deletions in rpoB have been identified, but point mutations in two codons, those coding for Ser531 and His526, are seen in about 70% of rifampin-resistant clinical isolates, with Ser531-to-Leu (TCG-to-TGG) mutations being by far the most common. To explore this phenomenon, we isolated independent, spontaneous, rifampin-resistant mutant versions of well-characterized M. tuberculosislaboratory strain H37Rv by plating 100 separate cultures, derived from a single low-density inoculum, onto rifampin-containing medium. Rifampin-resistant mutants were obtained from 64 of these cultures. Although we anticipated that the various point mutations would occur with approximately equal frequencies, sequencing the rpoBgene from one colony per plate revealed that 39 (60.9%) were Ser531 to Leu. We conclude that, for unknown reasons, the associated rpoB mutation occurs at a substantially higher rate than other rpoB mutations. This higher mutation rate may contribute to the high percentage of this mutation seen in clinical isolates.


1980 ◽  
Vol 37 (12) ◽  
pp. 2266-2271 ◽  
Author(s):  
Donald R. Gunderson

Theory on r-K selection is used as a basis for examining correlations between instantaneous rate of natural mortality (M), gonad-body weight index, age at maturity, longevity, and Bertalanffy growth parameters (k, L∞) for 10 species of marine fish. All correlations were consistent with r-K selection theory. The gonad-body weight index was found to be more highly correlated with M than any of the other life history parameters examined (r2 = 0.62), and stepwise multiple regression showed that additional variables added little to the predictive ability of the model. The gonad-body weight index appears to be quite useful in predicting M, and development of an analogous index on an energetics basis might enhance its utility in this regard.Key words: natural mortality, r-K selection, life history parameters


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