scholarly journals Development of Neurological Mouse Model for Toxoplasmosis Using Toxoplasma gondii Isolated from Chicken in Kenya

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
John Mokua Mose ◽  
David Muchina Kamau ◽  
John Maina Kagira ◽  
Naomi Maina ◽  
Maina Ngotho ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Mouse Model ◽  
Positive Control ◽  
Dexamethasone Treatment ◽  
Control Groups ◽  
Neuronal Necrosis ◽  
Outbred Mice ◽  
The Mean ◽  
The Brain

Animal models for the toxoplasmosis are scarce and have limitations. In this study, a neurological mouse model was developed in BALB/c mice infected intraperitoneally with 15 cysts of a Toxoplasma gondii isolate. The mice were monitored for 42 days and euthanized at different time points. Another group of mice were orally treated with dexamethasone (DXM: 2.66 mg/kg daily, 5.32 mg/kg daily) at 42 days after infection and monitored for a further 42 days. A mortality rate of 15% and 28.6% was observed in mice given 2.66 mg/kg/day and 5.32 mg/kg/day of DXM, respectively. The mean cyst numbers in the brain of DXM treated mice increased up to twofold compared with chronically infected untreated mice. Infections up to 42 days were associated with an increase in both IgM and IgG levels but following dexamethasone treatment, IgM levels declined but IgG levels continued on rising. The brain of toxoplasmosis infected mice showed mononuclear cellular infiltrations, neuronal necrosis, and cuffing. The severity of pathology was higher in mice treated with dexamethasone compared to the positive control groups. The findings of this study demonstrate that DXM-induced reactivation of chronic toxoplasmosis may be a useful development of laboratory animal model in outbred mice used for in vivo studies.

scholarly journals Effect of a Selective Progesterone Receptor Modulator on Induction of Apoptosis in Uterine Fibroids In Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Petr Horak ◽  
Michal Mara ◽  
Pavel Dundr ◽  
Kristyna Kubinova ◽  
David Kuzel ◽  
...  
Keyword(s):  
Uterine Fibroids ◽  
Premenopausal Women ◽  
Hormonal Treatment ◽  
Control Groups ◽  
Ulipristal Acetate ◽  
Receptor Modulator ◽  
Positive Clinical Effect ◽  
The Mean ◽  
And Control

Aim. To determine if hormonal treatment induces apoptosis in uterine fibroids.Methods. Immunohistochemical examination of fibroid tissue, using avidin-biotin complex and cleaved caspase-3 antibody for detecting apoptosis, was performed in premenopausal women who underwent 12-week treatment with oral SPRM (6 patients with 5 mg and 5 patients with 10 mg of ulipristal acetate per day) or gonadoliberin agonist (GnRHa, 17 patients) and subsequent myomectomy or hysterectomy for symptomatic uterine fibroids. Ten patients with no presurgical hormonal treatment were used as controls.Results. Apoptosis was present in a significantly higher proportion of patients treated with ulipristal acetate compared to GnRHa (P=0.01) and to patients with no hormonal treatment (P=0.01). In contrast to an AI of 158.9 in SPRM patients, the mean AI was 27.5 and 2.0 in GnRHa and control groups, respectively. No statistical difference in the AI was observed between the two groups of patients treated with ulipristal acetate (5 mg or 10 mg).Conclusion. Treatment with ulipristal acetate induces apoptosis in uterine fibroid cells. This effect of SPRM may contribute to their positive clinical effect on uterine fibroids.

Vasomotion of basilar arteries in vivo

1990 ◽  
Vol 258 (6) ◽  
pp. H1829-H1834 ◽  
Author(s):  
K. Fujii ◽  
D. D. Heistad ◽  
F. M. Faraci
Keyword(s):  
Moderate Hypertension ◽  
Vessel Diameter ◽  
Base Line ◽  
Large Artery ◽  
Cranial Window ◽  
Basilar Arteries ◽  
The Mean ◽  
Rhythmic Change ◽  
The Brain

Vasomotion is a rhythmic change in vascular caliber that has been described in vivo mainly in peripheral arterioles. In this study, we have characterized vasomotion in a large artery of the brain in vivo. In anesthetized rats, spontaneous vasomotion was observed in 38 of 47 basilar arteries visualized through a cranial window. Base-line arterial diameter was 259 +/- 9 (means +/- SE) microns. Under control conditions, the frequency of vasomotion was 4.8 +/- 0.2 cycles/min, and the amplitude was 19 +/- 2% of the mean diameter. Vasomotion usually occurred simultaneously along the entire length of the vessel, but in some arteries it propagated in either direction. Moderate hypertension (phenylephrine) or vasoconstriction induced by topical application of serotonin, vasopressin, or the thromboxane analogue U 46619 increased the frequency of vasomotion. Moderate hypotension or vasodilation induced by nitroglycerin, adenosine, or acetylcholine decreased the frequency. Marked hypertension, hypotension, or vasodilatation abolished vasomotion. Thus vasomotion of the basilar artery in vivo 1) is common and of relatively large amplitude, 2) does not seem to be driven by a single pacemaker, and 3) is dependent on vessel diameter or vasomotor tone.

scholarly journals A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
William J. Behof ◽  
Clayton A. Whitmore ◽  
Justin R. Haynes ◽  
Adam J. Rosenberg ◽  
Mohammed N. Tantawy ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mouse Model ◽  
Peripheral Tissues ◽  
Molar Activity ◽  
Model Of Alzheimer’S Disease ◽  
Specific Retention ◽  
5Xfad Mice ◽  
The Brain

AbstractErgothioneine (ERGO) is a rare amino acid mostly found in fungi, including mushrooms, with recognized antioxidant activity to protect tissues from damage by reactive oxygen species (ROS) components. Prior to this publication, the biodistribution of ERGO has been performed solely in vitro using extracted tissues. The aim of this study was to develop a feasible chemistry for the synthesis of an ERGO PET radioligand, [11C]ERGO, to facilitate in vivo study. The radioligand probe was synthesized with identical structure to ERGO by employing an orthogonal protection/deprotection approach. [11C]methylation of the precursor was performed via [11C]CH3OTf to provide [11C]ERGO radioligand. The [11C]ERGO was isolated by RP-HPLC with a molar activity of 690 TBq/mmol. To demonstrate the biodistribution of the radioligand, we administered approximately 37 MBq/0.1 mL in 5XFAD mice, a mouse model of Alzheimer’s disease via the tail vein. The distribution of ERGO in the brain was monitored using 90-min dynamic PET scans. The delivery and specific retention of [11C]ERGO in an LPS-mediated neuroinflammation mouse model was also demonstrated. For the pharmacokinetic study, the concentration of the compound in the serum started to decrease 10 min after injection while starting to distribute in other peripheral tissues. In particular, a significant amount of the compound was found in the eyes and small intestine. The radioligand was also distributed in several regions of the brain of 5XFAD mice, and the signal remained strong 30 min post-injection. This is the first time the biodistribution of this antioxidant and rare amino acid has been demonstrated in a preclinical mouse model in a highly sensitive and non-invasive manner.

scholarly journals Combination therapy with amphotericin B and fluconazole against invasive candidiasis in neutropenic-mouse and infective-endocarditis rabbit models.

1997 ◽  
Vol 41 (6) ◽  
pp. 1345-1348 ◽  
Author(s):  
H Sanati ◽  
C F Ramos ◽  
A S Bayer ◽  
M A Ghannoum
Keyword(s):  
Infective Endocarditis ◽  
Combination Therapy ◽  
Mouse Model ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Combined Therapy ◽  
Rabbit Model ◽  
Model Treatment ◽  
The Brain

Although there are an increasing number of new antifungal agents available, the morbidity and mortality due to invasive mycoses remain high. The high rates of polyene toxicities and the development of azole resistance have raised the issue of using antifungal agents of these classes in combination, despite theoretical concerns regarding antagonism between such agents. This study was designed to evaluate the in vivo efficacy of combined therapy with amphotericin B and fluconazole against Candida albicans. Two distinct animal models were used in this study: a neutropenic-mouse model of hematogenously disseminated candidiasis and the infective-endocarditis rabbit model. Treatment efficacy was assessed by determining reductions in mortality as well as decreases in tissue fungal densities. In the neutropenic-mouse model, amphotericin B, as well as combination therapy, significantly prolonged survival compared to untreated controls (P < 10(-5) and P = 0.001, respectively). The fungal densities in the kidneys of neutropenic mice were significantly reduced with either amphotericin B monotherapy or amphotericin B-fluconazole combined therapy compared to those of controls (P < 10(-6)). Fluconazole monotherapy also reduced fungal densities in the kidneys; however, this decrease was not statistically significant (P = 0.17). In contrast, treatment with either fluconazole alone or combined with amphotericin B (but not amphotericin B monotherapy) significantly decreased fungal densities in the brain (P = 0.025). In the rabbit endocarditis model, amphotericin B monotherapy or combined therapy significantly decreased fungal densities in cardiac vegetations (P < 0.01 versus the controls). Although no significant antagonism was seen when fluconazole was given in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B.

In vivo antimalarial activity and pharmacokinetics of artelinic acid-choline derivative liposomes in rodents

Parasitology ◽  
2019 ◽  
Vol 147 (1) ◽  
pp. 58-64
Author(s):  
Shuai Duan ◽  
Ruili Wang ◽  
Rongrong Wang ◽  
Jiaqi Tang ◽  
Xiaoyang Xiao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antimalarial Activity ◽  
Positive Control ◽  
Plasmodium Yoelii ◽  
Esterification Reaction ◽  
Therapeutic Effects ◽  
Control Groups ◽  
Time Curve ◽  
Survival Fraction

AbstractIt is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage against Plasmodium yoelii BY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes, P < 0.05) and other control groups (P ⩽ 0.05) at the doses of 4.4, 8.8, 17.6 µmol (kg·d)−1, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P < 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.

Ultrastructural Analysis of In Vivo Hypoglycemiant Effect of Two Polyoxometalates in Rats with Streptozotocin-Induced Diabetes

2015 ◽  
Vol 21 (5) ◽  
pp. 1236-1248 ◽  
Author(s):  
Ştefana Bâlici ◽  
Modeste Wankeu-Nya ◽  
Dan Rusu ◽  
Gheorghe Z. Nicula ◽  
Mariana Rusu ◽  
...  
Keyword(s):  
Diabetic Control ◽  
Diabetic Rats ◽  
Ultrastructural Analysis ◽  
Control Groups ◽  
Insulin Synthesis ◽  
Self Assembling ◽  
Insulin Granules ◽  
Streptozotocin Induced Diabetes ◽  
The Mean

AbstractTwo polyoxometalates (POMs), synthesized through a self-assembling method, were used in the treatment of streptozotocin (STZ)-induced diabetic rats. One of these nanocompounds [tris(vanadyl)-substituted tungsto-antimonate(III)-anions—POM1] was previously described in the literature, whereas the second [tris-butyltin-21-tungsto-9-antimonate(III)-anions—POM2], was prepared by us based on our original formula. In rats with STZ-induced diabetes treated with POMs (up to a cumulative dose of 4 mg/kg bodyweight at the end of the treatments), statistically significant reduced levels of blood glucose were measured after 3 weeks, as compared with the diabetic control groups (DCGs). Ultrastructural analysis of pancreatic β-cells (including the mean diameter of secretory vesicles and of their insulin granules) in the treated diabetic rats proved the POMs contribute to limitation of cellular degeneration triggered by STZ, as well as to the presence of increased amounts of insulin-containing vesicles as compared with the DCG. The two POMs also showed hepatoprotective properties when ultrastructural aspects of hepatocytes in the experimental groups of rats were studied. Based on our in vivo studies, we concluded that the two POMs tested achieved hypoglycemiant effects by preventing STZ-triggered apoptosis of pancreatic β-cells and stimulation of insulin synthesis.

Effect of Different Intermediary Bases on Microleakage of a Restorative Material in Class II Box Cavities of Primary Teeth

2017 ◽  
Vol 40 (2) ◽  
pp. 82-87 ◽  
Author(s):  
Faika Y. Abdelmegid ◽  
Fouad S. Salama ◽  
Waleed M. Al-Mutairi ◽  
Saud K. Al-Mutairi ◽  
Sultan O. Baghazal
Keyword(s):  
Primary Teeth ◽  
In Vitro Study ◽  
Class Ii ◽  
Positive Control ◽  
Negative Control ◽  
The Other ◽  
Control Groups ◽  
Significant Difference ◽  
The Mean

Introduction The aim of this in vitro study was to assess and compare the effect of different intermediary bases on microleakage between tooth and a nanocomposite interface in Class II box cavities in primary teeth. Methods Standard Class II box cavities were prepared in 52 primary molars and randomly divided into 9 groups according to the intermediary base used (Multicore Flow, Fuji II LC, SDR, Smart Dentin Replacement, and Biodentine). All specimens were subjected to thermocycling and prepared for microleakage testing and evaluation. Results There was significant difference in the mean ranks of microleakage between the 9 groups, which was observed in the gingival side (p<0.0001) and the occlusal side (p<0.0001). The mean ranks microleakage was significantly higher with experimental SDR, experimental Multicore Flow, and positive control materials when compared with the other 6 groups. The microleakage mean ranks were statistically significantly lower in experimental Fuji II LC, experimental Biodentine, and all negative control groups when compared with the other 3 groups. Conclusions Microleakage is affected by the application of intermediate material. Experimental Biodentine and Fuji II LC showed the lowest microleakage while experimental SDR and experimental Multicore Flow showed the highest microleakage.

scholarly journals In vivo activities of ceftriaxone and vancomycin against Borrelia spp. in the mouse brain and other sites.

1996 ◽  
Vol 40 (11) ◽  
pp. 2632-2636 ◽  
Author(s):  
R J Kazragis ◽  
L L Dever ◽  
J H Jorgensen ◽  
A G Barbour
Keyword(s):  
Body Weight ◽  
Lyme Disease ◽  
Positive Control ◽  
Negative Control ◽  
Scid Mice ◽  
Immunodeficient Mice ◽  
Infected Adult ◽  
The Brain

Borrelia burgdorferi, the agent of Lyme disease, and B. turicatae, a neurotropic agent of relapsing fever, are susceptible to vancomycin in vitro, with an MIC of 0.5 microgram/ml. To determine the activity of vancomycin in vivo, particularly in the brain, we infected adult immunocompetent BALB/c and immunodeficient CB-17 scid mice with B. burgdorferi or B. turicatae. The mice were then treated with vancomycin, ceftriaxone as a positive control, or normal saline as a negative control. The effectiveness of treatment was assessed by cultures of blood and brain and other tissues. Ceftriaxone at a dose of 25 mg/kg of body weight administered every 12 h for 7 to 10 days eliminated cultivable B. burgdorferi or B. turicatae from all BALB/c or scid mice in the study. Vancomycin at 30 mg/kg administered every 12 h was effective in eliminating infection from immunodeficient mice if treatment was started within 3 days of the onset of infection. If treatment with vancomycin was delayed for 7 days or more, vancomycin failed to eradicate infection with B. burgdorferi or B. turicatae from immunodeficient mice. The failure of vancomycin in eradicating established infections in immunodeficient mice was associated with the persistence of viable spirochetes in the brain during antibiotic treatment.

Vascular Abnormalities and Pulmonary Hypertension in the Berkeley Sickle Mouse.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3185-3185
Author(s):  
David R. Archer ◽  
Shawn Elms ◽  
Joshua Boutwell ◽  
Jennifer Perry ◽  
Roy Sutliff
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Endothelial Dysfunction ◽  
Mouse Model ◽  
Arterial Pressure ◽  
Right Ventricular ◽  
The Mean

Abstract Clinically, pulmonary hypertension is a major risk factor for mortality in adults with sickle cell disease. Contributing factors probably include red cell hemolysis and vaso-occlusive injury with their associated oxidative and inflammatory stimuli. Previously, we have described RBC hemolysis and endothelial oxidative stress in the Berkeley sickle mouse model and extend those studies in this work to investigate cardiovascular and endothelial dysfunction. Eight to ten month old homozygous and hemizygous Berkeley sickle mice and C57BL/6 control mice were used for all aspects of these experiments. In vivo measurements of mean arterial pressure and right ventricular pressures were conducted in fully anesthetized mice using a pressure transducer inserted in the carotid and right ventricle respectively. Following in vivo readings hearts were excised for measurement of ventricular mass. The ascending aorta was removed and cut into 5 mm rings for in vitro studies of agonist- induced contractility and relaxation. The mean arterial pressure of the hemizygous sickle mice (70.6 ± 3.4) was significantly lower than the control mice (86.0 ± 3.1) and the mean arterial pressure of homozygous sickle mice (59.0 ± 2.2 mmHg) was significantly lower than the hemizygous and control mice (p≤0.05 and p≤0.001, respectively). The right ventricular pressure showed a trend that approached significance (p= 0.08) such that pressures in homozygous mice were ≥ than those in hemizygous which were ≥ than those in control mice. Increased basal cardiac output was suggested by significant left ventricular hypertrophy. In vitro examination of potassium chloride activation of voltage gated calcium channels showed no significant difference in sensitivity or maximal contraction. Similarly, there was no difference in sensitivity to the α1 agonist, phenylephrine. However, both hemi- and homozygous mice showed a significant reduction in maximal force of contraction (normalized to cross sectional area when compared to controls. Maximal acetylcholine induced relaxation of aortic rings was significantly reduced (p≤0.05) in homozygous sickle mice compared to controls. The same effect was not seen with sodium nitroprusside induced relaxation indicating that the acetylcholine effect was not due to effects on the smooth muscle but was endothelium-dependent. The Berkeley mouse model shows cardiac hypertrophy consistent with the increased cardiac output associated with chronic anemia and a reduced basal mean arterial blood pressure similar to that seen in humans. 8–10 month old mice have increased right ventricular pressure and RV mass indicative of pulmonary hypertension. Further endothelial dysfunction is characterized by a reduction in the maximal relaxation elicited by acetylcholine. Therefore, the Berkeley mouse is a good model for investigating sickle related endothelial dysfunction.

scholarly journals AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse model of tauopathy

2017 ◽  
Vol 214 (5) ◽  
pp. 1227-1238 ◽  
Author(s):  
Christina Ising ◽  
Gilbert Gallardo ◽  
Cheryl E.G. Leyns ◽  
Connie H. Wong ◽  
Hong Jiang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Passive Immunization ◽  
Single Chain ◽  
Proinflammatory Response ◽  
Adeno Associated Virus ◽  
Single Chain Variable Fragments ◽  
Novel Strategy ◽  
Progressive Accumulation ◽  
The Brain

Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To investigate whether the Fc domain of HJ8.5 is required for the therapeutic effect, we engineered single-chain variable fragments (scFvs) derived from HJ8.5 with variable linker lengths, all specific to human tau. Based on different binding properties, we selected two anti-tau scFvs and tested their efficacy in vivo by adeno-associated virus–mediated gene transfer to the brain of P301S-tg mice. The scFvs significantly reduced levels of hyperphosphorylated, aggregated tau in brain tissue of P301S-tg mice, associated with a decrease in detergent-soluble tau species. Interestingly, these mice showed substantial levels of scFvs in the cerebrospinal fluid without significant effects on total extracellular tau levels. Therefore, our study provides a novel strategy for anti-tau immunotherapeutics that potentially limits a detrimental proinflammatory response.

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