EFFECTS OF SUBCHRONIC LEAD INTOXICATION ON THE MYOCARDIUM CONTRACTILITY OF RATS

2018 ◽  
pp. 22-32 ◽  
Author(s):  
B. A. Katsnelson ◽  
Yu. L. Protsenko ◽  
S. V. Klinova ◽  
O. N. Lookin ◽  
A. A. Balakin ◽  
...  
Keyword(s):  
Heart Function ◽  
Male Rats ◽  
Lead Intoxication ◽  
Passive Stiffness ◽  
Relaxation Cycle ◽  
Wide Range ◽  
Healthy Control ◽  
First Time ◽  
Lethal Doses

While it is known that chronic lead intoxication in humans induces arterial hypertension and thus can lead to some secondary disturbances of heart function, possible effects of this intoxication on myocardium contractility has never been proved. In our experiments outbred male rats were repeatedly injected IP with sub-lethal doses of lead acetate 3 times a week during 5 weeks. They developed an explicit even if moderate lead intoxication characterized by typical hematological and some other features. Next day after the last injection the heart of each animal was excised, and trabecules and papillary muscles from right ventricle were used for modeling in vitro isometric regimes of contraction-relaxation cycle. Several well-established parameters of this model proved to be changed as compared with preparations taken from hearts of healthy control rats. Against the background of in vivocalcium treatment both systemic and cardiotoxic effects of lead were somewhat attenuated. For the first time we showed that at subchronic intoxication with lead the myocardial preparations in a wide range of lengths react with decrease in their time and speed parameters of isometric contraction while keeping its amplitude, and with decrease in the passive stiffness of the trabecules. Features of the reaction of different structures of the heart and the shifting of isomyosin ratio to the slow isoform were demonstrated. Mechanistic and toxicological inferences from the results obtained are discussed.

scholarly journals Protective Effect of Opuntia dillenii Haw Fruit against Lead Acetate-Induced Hepatotoxicity: In Vitro and In Vivo Studies

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Reza Shirazinia ◽  
Ali Akbar Golabchifar ◽  
Vafa Baradaran Rahimi ◽  
Abbas Jamshidian ◽  
Alireza Samzadeh-Kermani ◽  
...  
Keyword(s):  
Cell Viability ◽  
Lead Acetate ◽  
Male Rats ◽  
Tnf Α ◽  
Wide Range ◽  
Hepatoprotective Effects ◽  
Anti Inflammatory ◽  
Opuntia Dillenii

Lead is one of the most common environmental contaminants in the Earth’s crust, which induces a wide range of humans biochemical changes. Previous studies showed that Opuntia dillenii (OD) fruit possesses several antioxidant and anti-inflammatory properties. The present study evaluates OD fruit hydroalcoholic extract (OHAE) hepatoprotective effects against lead acetate- (Pb-) induced toxicity in both animal and cellular models. Male rats were grouped as follows: control, Pb (25 mg/kg/d i.p.), and groups 3 and 4 received OHAE at 100 and 200 mg/kg/d + Pb (25 mg/kg/d i.p.), for ten days of the experiment. Thereafter, we evaluated the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), catalase (CAT) activity and malondialdehyde (MDA) in serum, and liver histopathology. Additionally, the cell study was also done using the HepG2 cell line for measuring the direct effects of the extract on cell viability, oxidative stress MDA, and glutathione (GSH) and inflammation tumor necrosis factor-α (TNF-α) following the Pb-induced cytotoxicity. Pb significantly increased the serum levels of ALT, AST, ALP, and MDA and liver histopathological scores but notably decreased CAT activity compared to the control group ( p < 0.001 for all cases). OHAE (100 and 200 mg/kg) significantly reduced the levels of serum liver enzyme activities and MDA as well as histopathological scores while it significantly increased CAT activity compared to the Pb group ( p < 0.001 –0.05 for all cases). OHAE (20, 40, and 80 μg/ml) concentration dependently and significantly reduced the levels of MDA and TNF-α, while it increased the levels of GSH and cell viability in comparison to the Pb group ( p < 0.001 –0.05 for all cases). These data suggest that OHAE may have hepatoprotective effects against Pb-induced liver toxicity both in vitro and in vivo by its antioxidant and anti-inflammatory activities.

scholarly journals In vivo and in vitro Volatile Constituents of the Flowers of Xylopia aromatica by HS‑SPME/GC-MS

2021 ◽  
Author(s):  
João Junqueira ◽  
Michelle do Nascimento ◽  
Lucas da Costa ◽  
Lincoln Romualdo ◽  
Francisco de Aquino ◽  
...  
Keyword(s):  
Solid Phase ◽  
Floral Scent ◽  
Principal Component ◽  
Gas Chromatography Mass Spectrometry ◽  
Large White ◽  
Volatile Constituents ◽  
Wide Range ◽  
First Time

Xylopia aromatica (Lam.) Mart. (Annonaceae) is a typical species from the Brazilian cerrado that presents medicinal properties. The plant is distinguished by its large white flowers which produce a pleasant fragrance. X. aromatica is characterized by a wide range of medicinal application. These characteristics have motivated us to investigate the flowers volatile organic compounds (VOCs) via in vivo and in vitro protocols by a headspace solid-phase microextraction (HS‑SPME) technique combined with gas chromatography-mass spectrometry (HS-SPME/GC‑MS). Four different fibers, extraction times and temperatures were the parameters changed to lead to the maximum profiling of the volatile constituents. Data were analyzed using principal component analysis (PCA). A total of 77 VOCs were extracted from the floral scent, with 52 and 68 extracted from in vivo and in vitro sampling, respectively, of which 48 were reported for the first time in the literature as volatile constituents from X. aromatica flowers. The extraction and identification of VOCs were successfully performed through HS-SPME/GC-MS. The PCA data allowed the identification of parameters that led to the maximum number of VOCs, which were polyacrylate (PA) and carboxen/polydimethylsiloxane (CAR/PDMS) fibers, 60 min extraction time and temperature of 29.0 °C. Among the volatile constituents identified, sesquiterpenes predominated, comprising about 61.04%.

scholarly journals Isolation and potential biocontrol of the fungus causing anthracnose in longan in Vietnam

2021 ◽  
Vol 24 (1) ◽  
pp. 1889-1896
Author(s):  
Phan Thi Huyen ◽  
Vo Thi Xuan Huong ◽  
Do Thanh Nhan
Keyword(s):  
Human Health ◽  
Economic Value ◽  
Culture Method ◽  
Fungal Species ◽  
Yield And Quality ◽  
Wide Range ◽  
Microbial Community Structures ◽  
Increasing Demand ◽  
First Time

Introduction: Longan is a crop plant of very high economic value, and both its fruit and flower are beneficial for human health. Longan has been increasingly cultivated in Vietnam due to the increasing demand for domestic consumption as well as export of its fruit. However, the widespread emergence and spread of anthracnose, a group of fungal disease affecting a wide range of plant species, in longan has seriously affected both the longan fruit yield and quality in Vietnam. Current methods for the prevention of anthracnose in longan depend mainly on the use of fungicides which are very harmful to human health as well as disruptive to microbial community structures in different ecosystems. In order to obtain an environmentally friendly method of control for this disease, the agent causing anthracnose in longan must first be identified. Therefore, the aim of this study was to isolate and identify the causal anthracnose agent in longan in Vietnam. Methods: Experiments were first carried out with pieces of anthracnose longan leaves pressed onto the surface of potato-dextrose agar (PDA) and incubated for days at 30◦C. Colonies, varying in appearance, were repeatedly isolated and purified on PDA agar, and the anthracnose-causing agent was initially recognized on the basis of colony characteristics and cell morphology. The suspected isolate was then tested for its ability to decompose healthy longan leaf in vitro, and its rDNA region was cloned and sequenced to determine its taxonomy. Antifungal activity testing was performed using the co-culture method. Results: We obtained a fungal isolate with septate hyphae, ovoid appressoria, and conidia (which were cylindrical in shape with rounded ends). This isolate showed a clear ability to decompose healthy longan leaves. At the molecular level, the isolate was determined to be a fungal species belonging to genus Colletotrichum, and therefore named Colletotrichum sp. strain BKHCM. We also found that its growth was inhibited when co-cultured with Streptomyces flaveus, an actinomycete originating from soil. Conclusion: For the first time, we isolated a fungal species belonging to genus Colletotrichum from anthracnose-infected longan leaves in Vietnam. We also showed that the growth of this fungus could potentially be biocontrolled.

Isolated hemoperfused heart model of slaughterhouse pigs

2001 ◽  
Vol 24 (4) ◽  
pp. 215-221 ◽  
Author(s):  
D. Modersohn ◽  
S. Eddicks ◽  
C. Grosse-Siestrup ◽  
I. Ast ◽  
S. Holinski ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Animal Experiments ◽  
Laboratory Animals ◽  
Coronary Perfusion ◽  
Balloon Catheters ◽  
Wide Range ◽  
Infusion Of Norepinephrine

A model of hemoperfused slaughterhouse pighearts is described providing a wide range of applications which leads to a reduction in animal experiments. The size of a pigheart, heart rate, coronary perfusion, metabolism, etc. are more comparable to conditions in patients than those in hearts of small laboratory animals. Global heart function can be assessed either by measuring stroke volume, ejection fraction, Emaxetc. in the working model or by measuring intraventricular pressure with balloon catheters in the isovolumetric model. Regional cardiac function can be measured by sonomicrometry and ischemic and non-ischemic areas can be compared. Local metabolic changes are measurable as well with microdialysis. Cardiac function can be kept on any given functional level by infusion of norepinephrine in spite of the fact that functional parameters are lower without adrenergic drive in vitro than in vivo. Stable heart function can be maintained for several hours with only 500 to 1000 ml of blood because the blood is permanently regenerated by a special dialysis system. This model can be applied in many research projects dealing with reperfusion injuries, inotropic, antiarrhythmic or arrhythmogenic effects of certain drugs, immunological rejection, evaluation of imaging systems (NMR, echocardiography etc.) or cardiac assist devices.

Abstract 14013: Direct Comparison of Disease-Specific versus TALEN-Corrected iPSC-Derived Cardiomyocytes from Dilated Cardiomyopathy Patients

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Antje Ebert ◽  
Johannes Riegler ◽  
Ioannis Karakikes ◽  
Vittavat Termglinchan ◽  
Mohammed Mameen ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Heart Function ◽  
Myocardial Infarct ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Transcription Activator ◽  
Significant Difference ◽  
Healthy Control

Introduction: Recent advances in regenerative medicine for cardiovascular disease (CVD) therapy focus on delivery of autologous induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to recover heart function without immunosuppression. Here, we perform a direct comparison of iPSC-CMs from a healthy individual, a DCM patient, and following genome-correction with transcription activator-like effector nucleases (TALENs) both in vitro and in vivo. Methods & Results: We established patient-specific iPSC-CMs that recapitulate DCM disease-phenotypes in-vitro, including disrupted sarcomeres and impaired Ca2+ handling (p<0.05). We corrected the patient′s DCM-specific mutation R173W in the TNNT2 locus via TALEN-mediated footprint-free genome editing. Isogenic TALEN-corrected iPSC-CMs recovered functional properties comparable to healthy control. Ca2+ transient analysis revealed no significant difference between TALEN-corrected iPSC-CMs and healthy control regarding amplitude (ΔF/F0 4.71±0.55), decay (277.6 ±28.2 ms), and time to peak (240.5±22.5 ms). Confocal microscopy of TALEN-corrected iPSC-CMs confirmed sarcomeric structures as in healthy control (Fig 1). We transplanted (i) 1x10*7 DCM iPSC-CMs, (ii) 1x10*7 TALEN-corrected iPSC-CMs, and (iii) 1x10*7 healthy control iPSC-CMs into a subacute myocardial infarct (MI) rat model (n=15/group). Cell engraftment into the host myocardium was confirmed by immunohistochemistry. Comprehensive functional analysis via magnetic resonance imaging (MRI), echocardiography is underway. Conclusions: We generated TALEN-corrected iPSC-CMs from a DCM patient, which recover in vitro functional parameters of healthy control iPSC-CMs. We transplanted for the first time patient-specific and TALEN-corrected iPSC-CMs into a rodent MI model. This approach may represent a viable option for mechanistic analysis and regenerative medicine in CVD patients. Figure 1:

scholarly journals Deep assessment of human disease-associated ribosomal RNA modifications using Nanopore direct RNA sequencing

2021 ◽  
Author(s):  
Isabel S Naarmann-de Vries ◽  
Christiane Zorbas ◽  
Amina Lemsara ◽  
Maja Bencun ◽  
Sarah Schudy ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Clinical Samples ◽  
Sequencing Data ◽  
Rna Modifications ◽  
Flow Cells ◽  
Wide Range ◽  
Catalytically Active ◽  
Induced Pluripotent ◽  
First Time

The catalytically active component of ribosomes, rRNA, is long studied and heavily modified. However, little is known about functional and pathological consequences of changes in human rRNA modification status. Direct RNA sequencing on the Nanopore platform enables the direct assessment of rRNA modifications. We established a targeted Nanopore direct rRNA sequencing approach and applied it to CRISPR-Cas9 engineered HCT116 cells, lacking specific enzymatic activities required to establish defined rRNA base modifications. We analyzed these sequencing data along with wild type samples and in vitro transcribed reference sequences to specifically detect changes in modification status. We show for the first time that direct RNA-sequencing is feasible on smaller, i.e. Flongle, flow cells. Our targeted approach reduces RNA input requirements, making it accessible to the analysis of limited samples such as patient derived material. The analysis of rRNA modifications during cardiomyocyte differentiation of human induced pluripotent stem cells, and of heart biopsies from cardiomyopathy patients revealed altered modifications of specific sites, among them pseudouridine, 2-O-methylation of ribose and acetylation of cytidine. Targeted direct rRNA-seq analysis with JACUSA2 opens up the possibility to analyze dynamic changes in rRNA modifications in a wide range of biological and clinical samples.

scholarly journals Spns2 Transporter Contributes to the Accumulation of S1P in Cystic Fibrosis Human Bronchial Epithelial Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1121
Author(s):  
Aida Zulueta ◽  
Michele Dei Dei Cas ◽  
Francesco Luciano ◽  
Alessandra Mingione ◽  
Francesca Pivari ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Mass Spectrometry Analysis ◽  
Bronchial Epithelial ◽  
Spectrometry Analysis ◽  
Healthy Control ◽  
Lung Biopsies ◽  
First Time ◽  
Excessive Accumulation

The role of S1P in Cystic Fibrosis (CF) has been investigated since 2001, when it was first described that the CFTR channel regulates the inward transport of S1P. From then on, various studies have associated F508del CFTR, the most frequent mutation in CF patients, with altered S1P expression in tissue and plasma. We found that human bronchial epithelial immortalized and primary cells from CF patients express more S1P than the control cells, as evidenced by mass spectrometry analysis. S1P accumulation relies on two- to four-fold transcriptional up-regulation of SphK1 and simultaneous halving of SGPL1 in CF vs. control cells. The reduction of SGPL1 transcription protects S1P from irreversible degradation, but the excessive accumulation is partially prevented by the action of the two phosphatases that are up-regulated compared to control cells. For the first time in CF, we describe that Spns2, a non-ATP dependent transporter that normally extrudes S1P out of the cells, shows deficient transcriptional and protein expression, thus impairing S1P accrual dissipation. The in vitro data on CF human bronchial epithelia correlates with the impaired expression of Spns2 observed in CF human lung biopsies compared to healthy control.

scholarly journals In VitroAntifungal Susceptibility of Candida glabrata to Caspofungin and the Presence ofFKSMutations Correlate with Treatment Response in an Immunocompromised Murine Model of Invasive Infection

2014 ◽  
Vol 58 (7) ◽  
pp. 3646-3649 ◽  
Author(s):  
Fabiola Fernández-Silva ◽  
Michaela Lackner ◽  
Javier Capilla ◽  
Emilio Mayayo ◽  
Deanna Sutton ◽  
...  
Keyword(s):  
Murine Model ◽  
Hot Spot ◽  
Drug Efficacy ◽  
Invasive Infection ◽  
Content Type ◽  
Wide Range ◽  
Systemic Infections ◽  
First Time

ABSTRACTIt has been argued that thein vitroactivity of caspofungin (CSP) is not a good predictor of the outcome of echinocandin treatmentin vivo. We evaluated thein vitroactivity of CSP and the presence ofFKSmutations in the hot spot 1 (HS1) region of theFKS1andFKS2genes in 17 Candida glabratastrains with a wide range of MICs. The efficacy of CSP against systemic infections from each of the 17 strains was evaluated in a murine model. No HS1 mutations were found in the eight strains showing MICs for CSP of ≤0.5 μg/ml, but they were present in eight of the nine strains with MICs of ≥1 μg/ml, i.e., three in theFKS1gene and five in theFKS2gene. CSP was effective for treating mice infected with strains with MICs of ≤0.5 μg/ml, showed variable efficacy in animals challenged with strains with MICs of 1 μg/ml, and did not work in those with strains with MICs of >1 μg/ml. In addition, mutations, including one reported for the first time, were found outside the HS1 region in theFKS2gene of six strains with different MICs, but their presence did not influence drug efficacy. Thein vitroactivity of CSP was compared with that of another echinocandin, anidulafungin, suggesting that the MICs of both drugs, as well as mutations in the HS1 regions of theFKS1andFKS2genes, are predictive of outcome.

scholarly journals Utilization of exogenous saccharides by protocorms of two terrestrial orchids  

2017 ◽  
Vol 63 (No. 4) ◽  
pp. 152-158
Author(s):  
Ponert Jan ◽  
Lipavská Helena
Keyword(s):  
Mycorrhizal Fungi ◽  
Life Strategy ◽  
Limited Knowledge ◽  
Phylogenetic Relations ◽  
Wide Range ◽  
Terrestrial Orchids ◽  
Time Utilization ◽  
First Time ◽  
Germination Stage

Orchid protocorms are completely mycoheterotrophic structures. Although saccharides are proposed as the main energy and carbon (C) sources provided by fungi, there is only limited knowledge on their effects. For the first time, utilization of a wide range of saccharides by in vitro axenic protocorms of two terrestrial orchids from two subfamilies, Ophrys iricolor subsp. lojaconoi and Oeceoclades, was tested. Protocorm size and, in the first of these also rhizoid length and soluble saccharide contents, were analysed. The endogenous saccharide spectra reflected the supplied saccharides and their metabolism. In both species, sucrose supported protocorm growth best. Surprisingly, fructose inhibited O. iricolor subsp. lojaconoi protocorm growth while O. decaryana ones grew well on it. Interestingly, mannitol abundant in mycorrhizal fungi was not utilized while sorbitol not found in fungi was usable. Galactose was toxic at pre-germination stage. Protocorm rhizoid length correlated with protocorm size but revealed several signalling effects of some saccharides. In conclusion, the orchid’s ability to utilize various saccharides reflects more likely species life strategy rather than phylogenetic relations or saccharide abundance in mycorrhizal fungi.  

scholarly journals VB1 Promoted Green Synthesis of Chalcones and its Neuroprotection Potency Evaluation

Processes ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 236 ◽  
Author(s):  
Yin ◽  
Shi ◽  
Wang ◽  
Liu ◽  
Ma
Keyword(s):  
P53 Protein ◽  
Glucose Deprivation ◽  
Neuroprotective Activity ◽  
High Yield ◽  
Thiamine Hydrochloride ◽  
Caspase 9 ◽  
Wide Range ◽  
Induced Apoptosis ◽  
First Time

For the first time, thiamine hydrochloride (VB1) has been employed as a catalyst for the synthesis of chalcones by metal-free Claisen–Schmidt condensation. Such an environmentally benign approach has several advantages such as a wide range of functional groups tolerance, a high yield of products, and the recoverability of this catalyst. Moreover, this unprecedented methodology enables the synthesis of the pharmaceutically important molecule 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (3f) and its derivatives. Moreover, 3f and its derivatives were screened for their preliminary in vitro neuroprotective activity against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis in SH-SY5Y cell lines. Most of the compounds exhibited the neuroprotective activity, and one of the prepared chalcones (3s), which incorporates prenyl moiety, showed the most potency by decreasing the expression of cleaved caspase-3, cleaved caspase-9, Bax, and p53 protein.

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