scholarly journals In Vivo Evaluation of the Nitroimidazole-Based Thioflavin-T Derivatives as Cerebral Ischemia Markers

2007 ◽  
Vol 2007 ◽  
pp. 1-5
Author(s):  
Taiwei Chu ◽  
Zejun Li ◽  
Xinqi Liu ◽  
Xiangyun Wang
Keyword(s):  
Cerebral Ischemia ◽  
Left Hemisphere ◽  
Thioflavin T ◽  
New Drugs ◽  
In Vivo Evaluation ◽  
Artery Ligation ◽  
Cerebral Ischemic ◽  
The Right ◽  
Thioflavin T Derivatives

Timely imaging and accurate interpretation of cerebral ischemia are required to identify patients who might benefit from more aggressive therapy, and nuclear medicine offers a noninvasive method for demonstrating cerebral ischemia. Three nitroimidazole-based thioflavin-T derivatives,N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl) propanamide (4NPBTA),N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl)-N-methylpropanamide (4NPBTA-1), andN-[4-(benzothiazol-2-yl)phenyl]-3-(2-nitroimidazole-1-yl) propanamide (2NPBTA), were radioiodinated and evaluated as possible cerebral ischemia markers. In normal mice, these compounds showed good permeation of the intact blood-brain barrier (BBB), high initial brain uptake, and rapid washout. In gerbil stroke models that had been subjected to right common carotid artery ligation to produce cerebral ischemia, [I131]2NPBTA, uptake in the right cerebral hemisphere decreased more slowly than that of the left, and the right/left hemisphere uptake ratios increased with time. Also, the right/left hemisphere uptake ratios correlated positively with the severity of the stroke. The results showed that [I131]2NPBTA had a specific location in the cerebral ischemic tissue. This represented a first step in finding new drugs and might provide a possible cerebral ischemic marker.

In Vivo Evaluation of Bioprinted Cardiac Patches Composed of Cardiac-Specific Extracellular Matrix and Progenitor Cells in a Model of Pediatric Heart Failure

2021 ◽  
Author(s):  
Donald Bejleri ◽  
Matthew Robeson ◽  
Milton Brown ◽  
Jervaughn Hunter ◽  
Joshua Maxwell ◽  
...  
Keyword(s):  
Heart Failure ◽  
Extracellular Matrix ◽  
Congenital Heart ◽  
Pediatric Patients ◽  
Heart Defects ◽  
In Vivo Evaluation ◽  
Surgical Methods ◽  
Pediatric Heart Failure ◽  
The Right

Pediatric patients with congenital heart defects (CHD) often present with heart failure from increased load on the right ventricle (RV) due to both surgical methods to treat CHD and the...

scholarly journals Carbonic anhydrase inhibition for the management of cerebral ischemia: in vivo evaluation of sulfonamide and coumarin inhibitors

2015 ◽  
Vol 31 (6) ◽  
pp. 894-899 ◽  
Author(s):  
Lorenzo Di Cesare Mannelli ◽  
Laura Micheli ◽  
Fabrizio Carta ◽  
Andrea Cozzi ◽  
Carla Ghelardini ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Carbonic Anhydrase ◽  
In Vivo Evaluation ◽  
Carbonic Anhydrase Inhibition

The Antibiotic Erythromycin Induces Tolerance against Transient Global Cerebral Ischemia in Rats (Pharmacologic Preconditioning)

2006 ◽  
Vol 104 (6) ◽  
pp. 1208-1215 ◽  
Author(s):  
Ansgar M. Brambrink ◽  
Ines P. Koerner ◽  
Kathrin Diehl ◽  
Georg Strobel ◽  
Ruediger Noppens ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Messenger Rna ◽  
Neuronal Cell ◽  
Tolerance Induction ◽  
Ischemic Tolerance ◽  
Global Cerebral Ischemia ◽  
Neuroprotective Effects ◽  
Transient Global Cerebral Ischemia ◽  
Cerebral Ischemic

Background Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression. Methods Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later. Results Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged. Conclusions Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.

scholarly journals In Vivo Evaluation of the Anti-Inflammatory Effect ofPistacia lentiscusFruit Oil and Its Effects on Oxidative Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Sameh Ben Khedir ◽  
Masarra Mzid ◽  
Sana Bardaa ◽  
Dorsaf Moalla ◽  
Zouheir Sahnoun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
New Drugs ◽  
Inflammatory Activity ◽  
Natural Health Products ◽  
Paw Edema ◽  
In Vivo Evaluation ◽  
Anti Inflammatory ◽  
Fruit Oil ◽  
Inflammatory Effect

In order to find new topical anti-inflammatory agents, we had recourse to a medicinal plant. This work was designed to determine the topical anti-inflammatory effect ofPistacia lentiscusfruit oil (PLFO), using carrageenan-induced paw edema rat model, and to evaluate its effects on oxidative stress. The topical anti-inflammatory activity of PLFO was compared to Inflocine® and estimated by measuring the diameter of paw edema, for 5 hours at a 1-hour interval. After that the rats were scarified and the inflamed paw tissue was removed for the exploration of some parameters of oxidative stress and histopathology. PLFO showed a significant anti-inflammatory activity in comparison with the Inflocine. The percentages of edema inhibition were 70% and % 51.5% (p<0.01), respectively, after five hours. The treatment with PLFO and Inflocine led to significant increases (p≤0.05) in the activities of CAT, SOD, and GPX and significant decreases in the MDA level and AOPP activity in the paw tissue after Carr injection, in comparison with the Carr group. Therefore, our findings demonstrate that PLFO might accelerate the development of new drugs which could be used scientifically as a source for natural health products in the treatment of topical inflammation.

scholarly journals An In Vitro Evaluation of the Diagnostic Quality Ultra-Speed Versus Insight Intraoral Dental Film

2004 ◽  
Vol 5 (4) ◽  
pp. 50-57 ◽  
Author(s):  
Thomas Schiff ◽  
Brandy Egan Solomon
Keyword(s):  
Faculty Members ◽  
Diagnostic Ability ◽  
In Vivo Evaluation ◽  
In Vitro Evaluation ◽  
Diagnostic Quality ◽  
Preference Criteria ◽  
Radiology Technicians ◽  
The Right

Abstract Twelve sets of FMS (full mouth survey) radiographs were taken by California licensed radiology technicians. Ten of the sets of FMS radiographs were taken using Ultra-Speed “D” film on the left side of the patient and Insight “F” speed film on the right side of the patient. The remaining two sets of films were taken using Insight Film on both sides of the patient to act as a control. Ten faculty members of the Diagnostic Department were asked to evaluate the twelve sets of FMS radiographs and report whether they had a preference for the right side, left side, or no preference. Criteria for preference were diagnostic ability and clarity of the films. The results of the study showed a preference for the right side (65.7%), which was imaged with Insight Film, compared to the left side (34.3%), which was imaged with Ultra-Speed Film. Citation Schiff T, Solomon BE. An In Vivo Evaluation of the Diagnostic Quality Ultra-Speed Versus Insight Intraoral Dental Film. J Contemp Dent Pract 2004 November;(5)4:050-057.

Abstract MP133: Development of β-arrestin-biased Positive Allosteric Modulators for the β 1 Adrenergic Receptor

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Jialu Wang ◽  
Ilhan Gokhan ◽  
Xinyu Xiong ◽  
Alem W Kahsai ◽  
Haoran Jiang ◽  
...  
Keyword(s):  
G Protein ◽  
Adrenergic Receptor ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
New Drugs ◽  
Artery Ligation ◽  
Biased Agonism ◽  
Receptor Biology ◽  
Induced Apoptosis

The β 1 adrenergic receptor (β 1 AR) is a central regulator of cardiac function and an important therapeutic target for cardiac diseases. Two emerging areas of receptor biology are biased agonism: ligand directed selective engagement of a receptor toward either a G protein or β-arrestin transducer; and allosteric modulation: ligands that bind to topographically distinct sites on the receptor to modulate its activity. Advances in these areas have the potential to yield new drugs that precisely enhance cardioprotective effects while limiting untoward detrimental actions. Compound 6 (Cmpd6) is a newly discovered positive allosteric modulator (PAM) for the β 2 AR. Interestingly, we now show that Cmpd6 has the unique property to enhance the binding affinity of the β-arrestin-biased agonist carvedilol to both the β 2 AR and the β 1 AR, while having minimal effect on the affinity of a panel of agonists and antagonists of the β 1 AR. We further tested the effect of Cmpd6 on β 1 AR signaling induced by a broad range of ligands. Cmpd6 selectively enhanced carvedilol-stimulated ERK activation in a β-arrestin-dependent signaling fashion, while having no effect on carvedilol-induced G protein-dependent cAMP production. To test the in vivo effect of Cmpd6 on cardiac injury, mice were pretreated with carvedilol with or without Cmpd6, then underwent ischemia/reperfusion through the left anterior descending artery ligation. Cell apoptosis was assessed by TUNEL. Carvedilol decreased the level of I/R-induced apoptosis compared to the vehicle-treated animals, and Cmpd6 significantly positively enhanced the anti-apoptotic effects of carvedilol. In conclusion, we identified Cmpd6 as a potential β-arrestin-biased PAM for the β 1 AR that enhances the cardioprotective effect of carvedilol. Ongoing studies will test Cmpd6 on heart failure post myocardial infarction.

scholarly journals Low-density lipoprotein receptor (LDLR) regulates NLRP3-mediated neuronal pyroptosis following cerebral ischemia/reperfusion injury

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Rui Sun ◽  
Mengna Peng ◽  
Pengfei Xu ◽  
Feihong Huang ◽  
Yi Xie ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Neurological Deficits ◽  
Density Lipoprotein Receptor ◽  
Cerebral Ischemic

Abstract Background Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemic stroke. NLRP3 inflammasome, involved in the regulation of inflammatory cascade, can simultaneously lead to GSDMD-executed pyroptosis in cerebral ischemia. Low-density lipoprotein receptor (LDLR), responsible for cholesterol uptake, was noted to exert potential anti-inflammatory bioactivities. Nevertheless, the role of LDLR in neuroinflammation mobilized by cerebral ischemia/reperfusion (I/R) has not been investigated. Methods Ischemic stroke mice model was accomplished by middle cerebral artery occlusion. Oxygen-glucose deprivation was employed after primary cortical neuron was extracted and cultured. A pharmacological inhibitor of NLRP3 (CY-09) was administered to suppress NLPR3 activation. Histological and biochemical analysis were performed to assess the neuronal death both in vitro and in vivo. In addition, neurological deficits and behavioral deterioration were evaluated in mice. Results The expression of LDLR was downregulated following cerebral I/R injury. Genetic knockout of Ldlr enhanced caspase-1-dependent cleavage of GSDMD and resulted in severe neuronal pyroptosis. LDLR deficiency contributed to excessive NLRP3-mediated maturation and release of IL-1β and IL-18 under in vitro and in vivo ischemic conditions. These influences ultimately led to aggravated neurological deficits and long-term cognitive dysfunction. Blockade of NLRP3 substantially retarded neuronal pyroptosis in Ldlr−/− mice and cultured Ldlr−/− neuron after experimental stroke. Conclusions These results demonstrated that LDLR modulates NLRP3-mediated neuronal pyroptosis and neuroinflammation following ischemic stroke. Our findings characterize a novel role for LDLR as a potential therapeutic target in neuroinflammatory responses to acute cerebral ischemic injury.

scholarly journals Chagas Disease Drug Discovery

2014 ◽  
Vol 20 (1) ◽  
pp. 22-35 ◽  
Author(s):  
Eric Chatelain
Keyword(s):  
Chagas Disease ◽  
New Technologies ◽  
Low Cost ◽  
Screening Strategy ◽  
New Drugs ◽  
In Vivo Models ◽  
The Right ◽  
The Impact

American trypanosomiasis, or Chagas disease, is the result of infection by the Trypanosoma cruzi parasite. Endemic in Latin America where it is the major cause of death from cardiomyopathy, the impact of the disease is reaching global proportions through migrating populations. New drugs that are safe, efficacious, low cost, and adapted to the field are critically needed. Over the past five years, there has been increased interest in the disease and a surge in activities within various organizations. However, recent clinical trials with azoles, specifically posaconazole and the ravuconazole prodrug E1224, were disappointing, with treatment failure in Chagas patients reaching 70% to 90%, as opposed to 6% to 30% failure for benznidazole-treated patients. The lack of translation from in vitro and in vivo models to the clinic observed for the azoles raises several questions. There is a scientific requirement to review and challenge whether we are indeed using the right tools and decision-making processes to progress compounds forward for the treatment of this disease. New developments in the Chagas field, including new technologies and tools now available, will be discussed, and a redesign of the current screening strategy during the discovery process is proposed.

Surface Area of Human Cerebral Cortex and Its Gross Morphological Subdivisions: In Vivo Measurements in Monozygotic Twins Suggest Differential Hemisphere Effects of Genetic Factors

1995 ◽  
Vol 7 (2) ◽  
pp. 292-302 ◽  
Author(s):  
Mark Jude Tramo ◽  
William C. Loftus ◽  
Catherine E. Thomas ◽  
Ronald L. Green ◽  
Leila A. Mott ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Surface Area ◽  
Left Hemisphere ◽  
Genetic Factors ◽  
Right Hemisphere ◽  
Monozygotic Twins ◽  
Cortical Surface ◽  
Cortical Surface Area ◽  
The Right

We measured the surEdce area of the cerebral cortex and its gross morphological subdivisions in 10 pairs of monozygotic twins. Cortical surface area was estimated in vivo using magnetic resonance imaging and threedimensional computer models of the intra- and extrasulcal pial surface. The means and standard deviations of regional (e.g., gyral), lobar, hemisphere, and total cortical surface area were tabulated for the entire population of 20 young, right-handed adults (10 females, 10 males). To determine whether genotypic differences were associated with morphometric differences, analyses of variance were carried out on each measure across unrelated twin pairs (genotype factor) and within co-twins (birth order factor). Across unrelated pairs, there was wide variation in regional cortical surface area for the left hemisphere (normalized by total cortical surface area, p ≤ 0.0001) but not for the right hemisphere (normalized, p = 0.12). More variation in lobar surface area was also observed for the left hemisphere (normalized, p = 0.05) than for the right (normalized, p = 0.48). Within co-twins, no signifcant variation in regional surface area or lobar surface area was found for the left or right hemisphere. Although normalized regional and lobar surface area in the left hemisphere differed across unrelated pairs, overall left hemisphere surface area normalized by total cortical surface area did not (p = 0.73). Total cortical surface area normallzed by body weight varied across unrelated pairs (p = 0.001) but not within co-twins (p = 0.39). The effects observed across unrelated pairs were not attributable to sex differences. These results suggest: 1) both the total area and folding of the cortical surface are heavily influenced by genetic factors in humans; and 2) the cerebral hemispheres may be differentially affected by genetic influences on cortical morphogenesis, with the languagedominant left cerebral cortex under stronger genetic control than the right.

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