Co-factor Influences the Severity of Zika Virus-Associated Microcephaly

Microcephaly has been regarded the most remarkable consequence of the Zika virus (ZIKV) epidemic in Brazil 2015. It remains to be determined whether there are factors that contribute to the degree of brain lesion associated with ZIKV infection during pregnancy. Previous studies showed that socioeconomic conditions correlate with ZIKV-associated microcephaly. Certain nutritional deficits display the potential to interfere in the mechanistic target of rapamycin (mTOR) signaling, which plays a major role in the pathophysiology of ZIKV-associated microcephaly. We hypothesize that a nutritional or environmental co-factor that interferes in mTOR signaling correlates with ZIKV-associated birth defects. To assess this hypothesis, we plan to: 1) develop a mouse model of ZIKV-associated microcephaly through intravenous injection of ZIKV and rapamycin for a straightforward interference on mTOR receptor; 2) determine in the experimental model and in cases of ZIKV-associated microcephaly the epigenetic signature (DNA methylation pattern) in neurons and muscle cells harvested by biopsy, and in hematopoietic and mesenchymal stem cells sorted from blood; 3) analyze through mass spectrometry in serum of pregnant female mice submitted to ZIKV and rapamycin injection and in serum of mothers of children with ZIKV-associated microcephaly the metabolomic pattern of cholesterol (a nutritional status marker), vitamin A and its metabolite retinoic acid, folate, and other metabolites related to these three nutritional factors; 4) check whether pregnant female mice submitted to intravenous injection of ZIKV and feed with a deficient diet of the most likely co-factor found in this study give birth to microcephalic mice with features that mimic clinical cases. In summary, our general objective is to develop an experimental model that mimics ZIKV-associated microcephaly cases and to find a co-factor involved in the microcephaly outbreak in Brazil 2015.

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Effect of glucocorticoids injected into pregnant female mice and rats on weight of male sexual glands in adult offspring and testosterone level in fetus in genotype-dependent

Cellular and Molecular Life Sciences ◽

10.1007/bf01919370 ◽

1994 ◽

Vol 50 (8) ◽

pp. 721-724 ◽

Cited By ~ 11

Author(s):

G. T. Shishkina ◽

N. N. Dygalo

Keyword(s):

Testosterone Level ◽

Pregnant Female ◽

Adult Offspring ◽

Female Mice ◽

Sexual Glands

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Zika Virus Serologic Diagnosis by NS1 ELISA in Curacao

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.698 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S302-S303 ◽

Cited By ~ 1

Author(s):

Samantha Manuel ◽

Liane Virginia-Cova ◽

Loubiela Joseph ◽

Chris Roggeveen ◽

Radjin Steingrover

Keyword(s):

Zika Virus ◽

Cross Reactivity ◽

Pregnant Female ◽

Serum Samples ◽

Zikv Infection ◽

Igm Elisa ◽

Pcr Diagnosis ◽

Two Samples ◽

Negative Controls

Abstract Background Zika virus (ZIKV) was introduced in the Caribbean island of Curacao in January 2016. A commercially available ZIKV IgM and IgG ELISA was evaluated on patients that were PCR-positive for ZIKV. Methods ZIKV infection was established by PCR in urine samples. Samples from PCR-positive patients were selected for validation of a ZIKV NS1 IgG and IgM ELISA. Patients with a follow-up sample ≥ 2 weeks after initial presentation were used to assess the sensitivity of the assay. Samples of 15 historical controls with serological evidence of Dengue, Chikungunya or an unrelated viral infection were included to establish specificity and cross-reactivity. Results Fourteen patients with positive ZIKV PCR diagnosis had repeated serum samples drawn ≥ 2 weeks after the initial sample. The combined results of these repeated IgM and IgG tests resulted in a sensitivity of 92%. One pregnant female showed no presence of IgG or IgM in any of the two samples. Testing of the panel of historical ZIKV-negative controls resulted in a specificity of 100% in both the quantitative and semi-quantitative setting of the ELISA. One patient with known high-titers of antibodies against Chikungunya virus in the respective panel displayed borderline reactive results for ZIKV IgG in both quantitative and semi-quantitative setting of the assay. Conclusion In this PCR-positive ZIKV cohort of patients, the newly available ZIKV NS1 ELISA displayed excellent performance characteristics. Cross-reactivity was indicated for Chikungunya in one case. No cross-reactivity was found for Dengue virus infection. One pregnant female showed no signs of developing anti-ZIKV IgM or IgG in this study. In the light of intrauterine pathogenesis, the lack of development of maternal IgG during ZIKV infection is a concern. Disclosures All authors: No reported disclosures.

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SIRT1 activator (SRT1720) improves the follicle reserve and prolongs the ovarian lifespan of diet-induced obesity in female mice via activating SIRT1 and suppressing mTOR signaling

Journal of Ovarian Research ◽

10.1186/s13048-014-0097-z ◽

2014 ◽

Vol 7 (1) ◽

Cited By ~ 36

Author(s):

Xiao-Ling Zhou ◽

Jin-Jie Xu ◽

Yan-Hong Ni ◽

Xiao-Chun Chen ◽

Hong-Xia Zhang ◽

...

Keyword(s):

Mtor Signaling ◽

Female Mice ◽

Diet Induced Obesity ◽

Sirt1 Activator

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Prevention of surgical infections in dogs with a single intravenous injection of marbofloxacin: an experimental model

Veterinary Record ◽

10.1136/vr.140.8.199 ◽

1997 ◽

Vol 140 (8) ◽

pp. 199-202 ◽

Cited By ~ 10

Author(s):

P. Gruet ◽

P. Richard ◽

E. Thomas ◽

A. Autefage

Keyword(s):

Experimental Model ◽

Intravenous Injection ◽

Single Intravenous Injection ◽

Surgical Infections

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Thermally Induced Convective Movements in a Standard Experimental Model for Characterization of Lesions Prior to Radiofrequency Functional Neurosurgery

Journal of Biomechanical Engineering ◽

10.1115/1.2401180 ◽

2006 ◽

Vol 129 (1) ◽

pp. 26-32

Author(s):

Joakim Wren ◽

Dan Loyd ◽

Urban Andersson ◽

Rolf Karlsson

Keyword(s):

Heat Flux ◽

Experimental Model ◽

Brain Lesion ◽

Maximum Velocity ◽

Patient Treatment ◽

Albumin Solution ◽

Functional Neurosurgery ◽

Final Size ◽

The Brain

Experimental exploration of equipment for stereotactic functional neurosurgery based on heating induced by radio-frequency current is most often carried out prior to surgery in order to secure a correct function of the equipment. The experiments are normally conducted in an experimental model including an albumin solution in which the treatment electrode is submerged, followed by a heating session during which a protein clot is generated around the electrode tip. The clot is believed to reflect the lesion generated in the brain during treatment. It is thereby presupposed that both the thermal and electric properties of the model are similar to brain tissue. This study investigates the presence of convective movements in the albumin solution using laser Doppler velocimetry. The result clearly shows that convective movements that depend on the time dependent heating characteristics of the equipment arise in the solution upon heating. The convective movements detected show a clear discrepancy compared with the in vivo situation that the experimental model tries to mimic; both the velocity (maximum velocity of about 5mm∕s) and mass flux are greater in this experimental setting. Furthermore the flow geometry is completely different since only a small fraction of the tissue surrounding the electrode in vivo consists of moving blood, whereas the entire surrounding given by the albumin solution in the experimental model is moving. Earlier investigations by our group (Eriksson et al., 1999, Med. Biol. Eng. Comput. 37, pp. 737–741; Wren, 2001, Ph.D. thesis; and Wren et al., 2001, Med. Biol. Eng. Comput. 39, pp. 255–262) indicate that the heat flux is an essential parameter for the lesion growth and final size, and that presence of convective movements in the model might substantially increase the heat flux. Thus, convective movements of the magnitude presented here will very likely underestimate the size of the brain lesion, a finding that definitely should be taken into consideration when using the model prior to patient treatment.

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A Dietary Vitamin B12 Deficiency Impairs Balance and Coordination After Ischemic Injury to the Sensorimotor Cortex in Adult Male and Female Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzab049_045 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 932-932

Author(s):

Gyllian Yahn ◽

Brandi Wasek ◽

Terry Bottiglieri ◽

Nafisa Jadavji

Keyword(s):

Risk Factor ◽

Ischemic Stroke ◽

Vitamin B12 ◽

Vitamin B12 Deficiency ◽

Stroke Outcome ◽

Deficient Diet ◽

Male And Female ◽

Female Mice ◽

B12 Deficiency ◽

Total Homocysteine

Abstract Objectives The majority of the world's population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain. Methods At 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid. Results All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet. Conclusions Vitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue. Funding Sources Midwestern University Start-Up Funds.

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The Effect of Folic Acid as Supportive Therapy of Spiramycine on Weight of Foetus to Toxoplasma gondii – Infected Pregnant Mice (Mus musculus)

Journal of Parasite Science ◽

10.20473/jops.v3i1.16432 ◽

2019 ◽

Vol 3 (1) ◽

pp. 33

Author(s):

Alfina Azkiana ◽

Boedi Setiawan ◽

Erma Safitri ◽

Lucia Tri Suwanti ◽

Mufasirin Mufasirin ◽

...

Keyword(s):

Folic Acid ◽

Toxoplasma Gondii ◽

Mus Musculus ◽

Supportive Therapy ◽

Pregnant Female ◽

Anova Test ◽

Analytical Balance ◽

Female Mice ◽

Pregnant Mice ◽

T1 And T2

This research aimed to investigate the effect of folic acid as supportive therapy of spiramycine on weight of foetus to Toxoplasma gondii-infected pregnant mice (Mus musculus). Twenty pregnant female mice were divided into four groups as C -, C +, T1 and T2. C +, T1 and T2 were infected by Toxoplasma gondii. C – and C + administered orally 0.5 ml aquadest, T1 administered orally 130 mg/kg BW spiramycine and 0.052 µg/g BW folic acid and T2 administered orally 0.052 µg/g BW folic acid. Experimental groups received the treatments for 5 days, then animals of each groups were sacrified. Foetuses were dissected out for observation. The weight of fetuses were measured using an analytical balance. The data weight of foetuses was presented descriptively and analyzed by ANOVA test and continued by Tukey HSD. From this study, the weight of foetuses from the pregnant mice of T1 and T2 have difference compared with the controls. The result of this research is folic acid affects the weight of foetuses to Toxoplasma gondii-infected pregnant mice.

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Tissue Factor Pathway Inhibitor Reduces Experimental Lung Metastasis of B16 Melanoma

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613114 ◽

2002 ◽

Vol 87 (06) ◽

pp. 930-936 ◽

Cited By ~ 60

Author(s):

Todd Meyer ◽

Jen-Yea Chang ◽

Mildred Amaya ◽

Farooq Siddiqui ◽

Hina Desai ◽

...

Keyword(s):

Tissue Factor ◽

Experimental Model ◽

Intravenous Injection ◽

Animal Studies ◽

Tissue Factor Pathway Inhibitor ◽

Expression Vector ◽

Tumor Biology ◽

Metastatic Activity ◽

Tissue Factor Pathway ◽

And Control

SummaryThe importance of tissue factor (TF) in tumor biology has been highlighted by studies suggesting its involvement in cell signaling, metastasis and angiogenesis. Since many animal studies have shown that anticoagulant therapy can reduce experimental metastasis, we studied whether the natural inhibitor of TF-mediated blood coagulation, Tissue Factor Pathway Inhibitor (TFPI), might be similarly effective. Using a murine experimental model, we found that intravenous injection of recombinant murine TFPI immediately before introduction of tumor cells reduced metastasis by 83% (P <0.001). B16 murine melanoma cells stably transfected with a TFPI expression vector exhibited reduced lung seeding following intravenous injection by 81% (P <0.001) compared with controls. No difference in primary tumor growth was observed between TFPI+ and control cells. Mice receiving intravenous somatic gene transfer of sense TFPI expression vector developed 78% fewer lung nodules than controls (P <0.05). We conclude that TFPI has significant anti-metastatic activity in this experimental model.

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