Adsorption and bacterial performance of Nd2O3 modified Ag nanoparticles with enhanced degradation of methylene blue.

Our study focused on the optical behavior, methylene blue (MB) dye degradation potential, antibacterial performance, and silver and trioxide mineral interaction with different bacterial species. We found that the addition of silver nanoparticles (Ag NPs) to neodymium oxide (Nd2O3) resulted in a significant response, with an enlargement of the inhibition zone for bacterial species such as Staphylococcus aureus and Escherichia coli. Specifically, the inhibition zone for S. aureus increased from 9.3 ± 0.5 mm for pure Nd2O3 to 16.7 ± 0.4 mm for the Ag/Nd2O3 nano-composite, while for E. coli, it increased from 8.8 ± 0.4 mm for Nd2O3 to 15.9 ± 0.3 mm for Ag/Nd2O3. Furthermore, the optical behavior of the composites showed a clear band-gap narrowing with the addition of Ag NPs, resulting in enhanced electronic localization. The direct and indirect transitions reduced from 6.7 to 6.1 eV and from 5.2 to 2.9 eV, respectively. Overall, these results suggest that the Ag/Nd2O3 nano-composite has potential applications in sensor industries and water treatment, thanks to its enhanced optical behavior, antibacterial performance, and efficient MB degradation capabilities. In terms of MB degradation, the Ag/Nd2O3 mixed system exhibited more efficient degradation compared to pure Nd2O3. After 150 min, the MB concentration in the mixed system decreased to almost half of its starting point, while pure Nd2O3 only reached 33%.

The emerging role of lipid nanosystems and nanomicelles in liver diseases.

Nanoparticles (NPs) exhibit remarkable potential in the diagnosis and treatment of various liver ailments, including primary liver cancer or hepatocellular carcinoma (HCC), liver cirrhosis, viral hepatitis, and alcoholic and non-alcoholic liver diseases. High surface area-to-volume ratio with distinct physicochemical and bio-pharmaceutical properties have contributed numerous benefits to NPs, such as high intracellular uptake and efficient drug delivery capabilities stemming from their ability to encapsulate a diverse range of drugs. Lipid-based nanosystems have demonstrated significant potential as reliable and efficient transport vehicles for a variety of actives, including small interfering RNA, targeting the liver, owing to their excellent in vivo compatibility, biodegradable nature, and non-toxic properties. Multiple aspects of various lipid-based materials, lipid nanosystems like solid lipid NPs, nanovesicles such as nanoemulsions, liposomes, and nanomicelles for liver-specific active targeting have been comprehensively reviewed. Ongoing and completed clinical trials of lipid nanosystems developed for HCC, hepatic fibrosis, and hepatitis are tabulated. Types of receptors and ligands typically used for active liver targeting in HCC are extensively discussed. The US FDA's recent approval for the use of Onpattro (Patisiran) injection to treat polyneuropathy in adult patients is indicative of the rapid development of lipid nanosystems employed for hepatic targeting. Nanoemulsions loaded with diagnostic imaging agents for multi-modal liver imaging were briefly discussed. Emerging technologies are being developed to integrate desirable properties of nanoparticles (NPs), including high stability, efficient drug loading, opsonization avoidance, active liver targeting, and facilitation of endosomal escape. Clinical translations of many lipid NPs for drug and gene therapy applications targeting different liver diseases are expected in the near future.

Hepaticojejunostomy with gastric access loop versus conventional hepaticojejunostomy: a randomized trial.

Roux-en-Y hepaticojejunostomy (RYHJ) with the provision of "gastric access loop" was developed to shorten the distance traveled by the endoscope to reach hepaticojejunostomy (HJ) anastomotic site. The aim of our study was to assess modified RYHJ with gastric access loop (RYHJ-GA) and compare it with conventional RYHJ (RYHJ-C) regarding short- and long-term outcomes and, moreover, to evaluate the feasibility and results of future endoscopic access of the modified bilio-enteric anastomosis. Patients eligible for RYHJ between September 2017 and December 2019 were allocated randomly to receive either RYHJ-C or RYHJ-GA. Fifty-two patients were randomly assigned to RYHJ-C (n = 26) or RYHJ-GA (n = 26). Three cases in RYHJ-C and 4 cases in RYHJ- GA developed HJ anastomotic stricture (HJAS) (P=0.68). 3 cases of RYHJ-GA had successful endoscopic dilation and balloon sweeping of biliary mud (one case) or stones (2 cases). Revisional surgery was needed in 2 cases of RYHJ-C and 1 case in RYHJ-GA (P=0.68). Modified RYHJ with gastric access loop is comparable to the classic hepaticojejunostomy regarding complications. However, gastric access enables easy endoscopic access for the management of future HJAS. This modification should be considered in patients with a high risk of HJAS during long-term follow-up.The trial registration number (TRN) and date of registration:ClinicalTrials.gov (NCT03252379), August 17, 2017.

Physical and biological changes of copper oxide and hydroxyapatite filled in polycaprolactone scaffolds: Cellular growth behavior and antibacterial activity.

Burns have placed a devastating burden on public health because of leading to an increased risk of infection. Therefore, the development of an effective antibacterial dressing for wound healing is essential. The present work is mainly based on the fabrication of biodegradable polycaprolactone (PCL) films through a simple and cheap process of polymer casting using a novel combination of hydroxyapatite (HAP), cuprous oxide (Cu2O) NPs and graphene oxide (GO) nanosheets which have a great effect in preventing colonization and to modify the wound dreasing. The compositions played a key role in decreasing the contact angle of PCL from 47.02° to 11.53°. Further, the cell viability exhibited a viable cell ratio of 81.2% after 3 days of culturing. Moreover, the highest antibacterial activity was obtained from the film of Cu2O@PCl and showed high impact results in antibacterial behavior.

Pregnenolone protects the liver against doxorubicin-induced cellular injury by anti-inflammatory, antioxidant, and antiapoptotic mechanisms: role of Keap1/Nrf2/HO-1 and P-glycoprotein.

OBJECTIVE: Doxorubicin (DOX) is a widely used cytotoxic anthracycline antibiotic characterized by increased adverse effects that limit its clinical usefulness. Pregnenolone is a pregnane X receptor (PXR) agonist that increases the expression of xenobiotic transporters with anti-inflammatory and antioxidant potential. Thus, we hypothesized that pregnenolone would protect against DOX-induced hepatotoxicity. MATERIALS AND METHODS: Male Wistar rats (180-200 g) were randomized into four groups (n = 7): Control, Control + Pregnenolone (35 mg/kg/day, orally), DOX (15 mg/kg, i.p.) single dose on day five, and Pregnenolone + DOX. All treatments continued for seven consecutive days. Twenty-four hours after the last treatment, serum and liver tissues were collected for biochemical and histopathological assessment. The possible interaction between pregnenolone and DOX on cell viability was tested in HepG2 cells in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: DOX treatment resulted in hepatic damage and fibrosis with increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver samples of the DOX-treated group showed increased oxidative stress [malondialdehyde (MDA) and total nitrite/nitrate and decreased reduced glutathione (GSH) and superoxide dismutase (SOD)], increased hepatic tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-ß1), and mRNA of interleukin-1beta (IL-1ß) and interleukin-6 (IL-6). Pretreating the rats with pregnenolone antagonized these DOX-induced effects. Moreover, pregnenolone upregulated the hepatic expression of Nrf2, heme oxygenase-1 (HO-1), and P-glycoprotein and decreased Keap1, opposing the effects of DOX. Moreover, pregnenolone prevented the DOX-induced activation and nuclear translocation of NFκB and increased cleaved caspase-3. Pregnenolone potentiated DOX-mediated cytotoxicity in HepG2 cells. CONCLUSIONS: These results illustrate the protective effects of pregnenolone against DOX-induced hepatotoxicity without limiting its anticancer activity.

Therapeutic Role of Subcutaneous Access Loop Created Adjunct to Hepaticojejunostomy for Management of Bile Duct Injury.

BACKGROUND: Roux-en-Y hepaticojejunostomy (RYHJ) is usually required for major bile duct injury (BDI) as a definitive treatment. Hepaticojejunostomy anastomotic stricture (HJAS) is the most feared long-term complication following RYHJ. The ideal management of HJAS remains undefined. The provision of permanent endoscopic access to the bilio-enteric anastomotic site can make endoscopic management of HJAS feasible and attractive option. In this cohort study, we aimed to evaluate short- and long-term outcomes of subcutaneous access loop created adjunct to RYHJ (RYHJ-SA) for management of BDI and its usefulness for endoscopic management of anastomotic stricture if occurred. MATERIALS AND METHODS: This is a prospective study including patients who were diagnosed with iatrogenic BDI and underwent hepaticojejunostomy with subcutaneous access loop between September 2017 and September 2019. RESULTS: This study included a total number of 21 patients whom ages ranged between 18 and 68 years. During follow-up, three cases had HJAS. One patient had the access loop in subcutaneous position. Endoscopy was done but failed to dilate the stricture. The other 2 patients had the access loop in subfascial position. Endoscopy of them failed to enter the access loop due to failure of fluoroscopy to identify the access loop. The three cases underwent redo-hepaticojejunostomy. Parajejunal (parastomal) hernia occurs in 2 patients in whom the access loop was fixed subcutaneous position. CONCLUSION: In conclusion, modified RYHJ with subcutaneous access loop (RYHJ-SA) is associated with reduced quality of life and patient satisfaction. Moreover, its role in endoscopic management of HJAS after biliary reconstruction for major BDI is limited.

Venoms classification and therapeutic uses: a narrative review.

The mere glimpse of venomous animals has always terrified humans because of the devastating effects of their venoms. However, researchers across the globe have isolated therapeutically active ingredients from these venoms and continue to explore them for drug leads. These efforts lead to the discovery of therapeutic molecules that the US-FDA has approved to treat different diseases, such as hypertension (Captopril), chronic pain (Ziconotide), and diabetes (Exenatide). The main active constituents of most venoms are proteins and peptides, which gained more attention because of advancements in biotechnology and drug delivery. The utilization of newer screening approaches improved our understanding of the pharmacological complexity of venom constituents and facilitated the development of novel therapeutics. Currently, with many venom-derived peptides undergoing different phases of clinical trials, more are in pre-clinical drug development phases. This review highlights the various sources of venoms, their pharmacological actions, and the current developments in venom-based therapeutics.

Optical, Thermal, and Electrical Characterization of Polyvinyl Pyrrolidone/Carboxymethyl Cellulose Blend Scattered by Tungsten-Trioxide Nanoparticles.

The polymeric material polyvinyl pyrrolidine/carboxymethyl cellulose (PVP/CMC) was mixed with different quantities of tungsten-trioxide nanoparticles (WO3 NPs). The samples were created using the casting method and Pulsed Laser Ablation (PLA). The manufactured samples were analyzed by utilizing various methods. The halo peak of the PVP/CMC was located at 19.65°, confirming its semi-crystalline nature, as shown in the XRD analysis. FT-IR spectra of pure PVP/CMC composite and PVP/CMC composite incorporated with various contents of WO3 obtained a shift in band locations and change in intensity. Optical band gap was calculated via UV-Vis spectra, which decreased when increasing the laser-ablation time. Thermogravimetric analyses (TGA) curves showed that samples' thermal stability had improved. The frequency-dependent composite films were used to determine AC conductivity of the generated films. When increasing the content of tungsten-trioxide nanoparticles, both (ε') and (ε'') increased. The incorporation of tungsten trioxide enhanced the ionic conductivity of PVP/CMC/WO3 nano-composite to a maximum of 10-8 S/c. It is expected that these studies will have a significant impact on several utilizations, such as energy storage, polymer organic semiconductors, and polymer solar cells.

Fenofibrate ameliorates letrozole-induced polycystic ovary in rats via modulation of PPARα and TNFα/CD95 pathway.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a prevalent endocrine health problem during the childbearing period that seriously affects fertility in females. Fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, showed beneficial effects in models of endocrine disturbances. Thus, we evaluated the potential therapeutic effect of fenofibrate in experimental PCOS. MATERIALS AND METHODS: Rats received oral fenofibrate (300 mg/kg/day) for three weeks following a three-week PCOS induction regimen using oral letrozole (1 mg/kg/day). We determined the changes in body weight, levels of serum testosterone, insulin, anti-Müllerian hormone (AMH), ovarian malondialdehyde (MDA), superoxide dismutase (SOD), and tissue tumor necrosis factor-alpha (TNFα) and CD95 protein expressions. The tissue expression of interleukin-10 (IL10) and PPARα genes was determined. RESULTS: Letrozole-treated rats showed successful induction of PCOS, confirmed by histopathology and significantly increased body weight, testosterone, insulin, AMH, and MDA, and decreased SOD. Ovaries of untreated PCOS rats showed increased TNFα and CD95 and decreased PPARα and IL10 expression. Administration of fenofibrate ameliorated the letrozole-induced PCOS changes. CONCLUSIONS: Fenofibrate-mediated amelioration of PCOS in rats is attributed partly to its antioxidant, anti-inflammatory, and anti-apoptotic properties and activation of PPARα.

The incidence of significant pathology in patients presenting with benign-appearing unilateral nasal polyps.

OBJECTIVE: The presentation of unilateral nasal polyps traditionally necessitates histological evaluation for a neoplasm. This study sought to determine the rates of significant pathology in patients presenting with benign-appearing unilateral nasal polyps, to inform practice. METHOD: All patients who underwent nasal polypectomy for benign-appearing unilateral nasal polyps over a 13-year period were included. RESULTS: A total of 77 patients were included. On histology, 60 cases (77.9 per cent) were found to be inflammatory polyps. Thirteen cases were neoplastic, of which 11 (14.3 per cent) were benign and 2 (2.6 per cent) were malignant neoplasms. The following significant pathologies were found: Schneiderian papillomas, in 10 cases (13.0 per cent); neurofibroma, in 1 case (1.3 per cent); adenoid cystic carcinoma, in 1 case (1.3 per cent); and malignant melanoma, in 1 case (1.3 per cent). CONCLUSION: Our data support routine histological assessment for all unilateral nasal polyps. Malignancy is rare (2.6 per cent) in patients presenting with benign-appearing unilateral nasal polyps. In elderly, unfit patients with minimal symptoms, initial conservative management may be reasonable.

Compositional characteristics of dairy products and their potential nondairy applications after shelf-life.

Many dairy products are discarded and useless after end of shelf-life, which causes economic and environmental challenges. The objective of this study was to study the compositional characteristics of some dairy products before and after shelf-life, and develop a process to utilize those dairy products after end of shelf-life in non dairy applications (cosmetic cream and soap). Several dairy products, such as sterilized milk, yogurt, soft cheese, hard cheese, cream, and butter were collected from markets in Egypt before shelf-life and after three months of shelf-life. Electrophoresis analysis was conducted to estimate the changes in the protein fractions of protein products (sterilized milk, yogurt, and cheese) before and after expiration. Also, gas chromatography (GS) was performed to compare the fatty acids of fat products (cream and butter) before and after end of shelf-life. Sterilized milk, yogurt, soft, and hard cheese were turned into powder (Expired dairy products powder; EDPP) to be used as a raw material in manufacturing of cosmetic creams. The fat was separated from cream, butter, and hard cheese (Expired dairy products fat; EDPF) to be utilized in making soap. The formulated cosmetic creams were examined in vitro. Functional properties of cream were determined, such as appearance, spreadability, irritancy, and pH. Additionally, the soap quality was tested after manufacture. We found that dairy products, such as milk, yogurt, and cheese after shelf-life can be utilized as raw materials for the production of cosmetic creams, as well as production of soap from butter and cream. The produced products were similar to those in commercial markets. This study is an endeavor to conquer the dairy industry challenges, which are considered a huge loss from the economic and environmental aspects.

Vanadyl sulphate ameliorates biomarkers of endothelial injury and coagulation and thrombosis in a rat model of hyperglycaemia.

BACKGROUND: We sought to determine whether the insulin mimicking agent, vanadyl sulphate (Van) can inhibit biomarkers of endothelial injury and coagulation and thrombosis induced by a moderate level of hyperglycaemia. MATERIAL AND METHODS: Hyperglycaemia was induced in rats by a single injection of streptozotocin (STZ, 50 mg/kg) two weeks after being fed on a high-fat diet (model group). The treatment group started Van (20 mg/kg/day) treatment one-week post STZ injection and continued on Van until being sacrificed at week 10. RESULTS: Administration of Van to the model group significantly (p < .05) ameliorated dyslipidemia and biomarkers of inflammation (TNF-α, IL-6, and hsCRP) and endothelial injury (E-selectin, P-selectin, sICAM-1, sVCAM-1, and ET-1). Van also significantly inhibited hyperglycaemia-induced blood levels of coagulation (vWF) and thrombosis (PAI-1 and fibrinogen) biomarkers. CONCLUSIONS: Vanadyl sulphate effectively suppresses hyperglycaemia-induced endothelial injury, coagulation and thrombosis, which is associated with the inhibition of inflammation and dyslipidemia.

Can we improve our day-case rate in functional endoscopic sinus surgery?

OBJECTIVE: Day-case functional endoscopic sinus surgery is associated with increased patient satisfaction and reduced costs. This study aimed to identify reasons for overnight admission with a view to improving same-day discharge. METHODS: This was a retrospective observation study over a one-year period. All consecutive patients who underwent elective functional endoscopic sinus surgery were included. RESULTS: A total of 172 patients were included in this study. Functional endoscopic sinus surgery was planned as a day-case procedure in 152 patients (88 per cent), with a planned overnight stay in 20 (12 per cent). The rate of same-day discharge in patients who underwent elective functional endoscopic sinus surgery was 80.2 per cent (n = 138). Reasons for an unplanned overnight admission were: bleeding (n = 8), urinary retention (n = 3), medical co-morbidities (n = 1), post-operative pain (n = 1) and social reasons (n = 1). CONCLUSION: There is scope to further improve the functional endoscopic sinus surgery day-case rate by utilising techniques to minimise post-operative bleeding. This has the potential to improve both patient satisfaction and service efficiency.

Acylated Ghrelin Administration Inhibits Sleeve Gastrectomy-Induced Hippocampal Oxidative Stress, Apoptosis and Tau-Hyperphosphorylation by Activating the PI3K/Akt Pathway.

This study investigated the impact of exogenous replacement therapy with acylated ghrelin (AG) post sleeve gastrectomy (SG) on the memory function in rats. In addition, we investigated the possible underlying mechanisms, including the effects on markers of oxidative stress, tau phosphorylation, and apoptosis. Adult male Wistar rats were divided into four groups (N = 18/group) as follows: sham (control), SG, SG+AG (100 µM), and SG+AG+LY294002 (0.25 µg/100 g). We continued all treatments daily for four weeks post-surgery. SG impaired the spatial, retention, and recognition memories as tested by the Morris water maze test, passive avoidance test, and novel object recognition test, respectively. Also, it enhanced the levels of reactive oxygen species and lipid peroxides, reduced glutathione and protein levels of Bcl-2, and increased the levels of Bax and cleaved caspase-3 in the hippocampus. In addition, SG reduced the hippocampal levels of acetylcholine and brain-derived neurotrophic factor. Concomitantly, it inhibited the hippocampal activity of Akt and increased the activity of glycogen synthase kinase 3ß and tau protein phosphorylation. Exogenous administration of acylated ghrelin to rats that had undergone SG prevented memory deficits. Also, it prevented the alteration in the above-mentioned biochemical parameters, an effect that was abolished by co-administration of LY294002 (phosphoinositide 3-kinase inhibitor). In conclusion, AG replacement therapy after SG in rats protects them against memory deficits and hippocampal damage by suppressing tau protein phosphorylation, mediated by activating PI3K/Aktinduced inhibition of glycogen synthase kinase 3ß.

Numerical and experimental study on turbulence statistics in a large fan-stirred combustion vessel.

ABSTRACT: Particle image velocimetry (PIV) has become a popular non-intrusive tool for measuring various types of flows. However, when measuring three-dimensional flows with two-dimensional (2D) PIV, there are some uncertainties in the measured velocity field due to out-of-plane motion, which might alter turbulence statistics and distort the overall flow characteristics. In the present study, three different turbulence models are employed and compared. Mean and fluctuating fields obtained by three-dimensional computational fluid dynamics modeling are compared to experimental data. Turbulence statistics such as integral length scale, Taylor microscale, Kolmogorov scale, turbulence kinetic energy, dissipation rate, and velocity correlations are calculated at different experimental conditions (i.e., pressure, temperature, fan speed, etc.). A reasonably isotropic and homogeneous turbulence with large turbulence intensities is achieved in the central region extending to almost 45 mm radius. This radius decreases with increasing the initial pressure. The influence of the third dimension velocity component on the measured characteristics is negligible. This is a result of the axisymmetric features of the flow pattern in the current vessel. The results prove that the present vessel can be conveniently adopted for several turbulent combustion studies including mainly the determination of turbulent burning velocity for gaseous premixed flames in nearly homogeneous isotropic turbulence.

The impact of concomitant administration of vanadium and insulin on endothelial dysfunction markers (PAI-1 and ET-1) in type 1 diabetic rats.

Endothelial dysfunction in type 1 diabetes mellitus (T1DM) is an important factor in the pathogenesis of micro- and macrovascular complications. The present study was to investigate the impact of combined vanadium and insulin for proper control and protection against endothelial dysfunction in T1DM rats. Sixty male Sprague-Dawley rats were randomly divided into six groups; control non-treated; control vanadium treated; T1DM; T1DM + insulin; T1DM + vanadium; T1DM + insulin + vanadium treated groups. At the end of the experiment (6 weeks), serum C-reactive protein, tumour necrosis factor-alpha, IL-6, endothelin-1, plasminogen activator inhibitor-1, fasting glucose serum lipogram, liver homogenate SOD activity and MDA levels were determined. Concomitant insulin and vanadium treatment improved the diabetic metabolic disturbances in addition to endothelial dysfunction and inflammatory markers. We can conclude that concomitant administration of both vanadium and insulin in T1DM decreased the risk for the development of endothelial dysfunction, micro- and macrovascular complications.

Insulin protects against type 1 diabetes mellitus-induced aortopathy associated with the inhibition of biomarkers of vascular injury in rats.

BACKGROUND: We sought to investigate the protective effect of insulin against type 1 diabetes mellitus (T1DM)-induced aortic injury (aortopathy) associated with the inhibition of biomarkers of vascular injury. MATERIAL AND METHODS: T1DM was induced in rats by streptozotocin (STZ) (65 mg/kg), and the protection group started insulin treatment 2 days post diabetic induction and continued until being sacrificed at week 8. RESULTS: Aortopathy was developed in the diabetic rats as demonstrated by profound alterations to the aorta ultrastructure, which was substantially protected by insulin. In addition, insulin significantly inhibited diabetes-induced dyslipidaemia, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1), oxidative stress, and inflammation. However, blood levels of these biomarkers in the insulin-treated group were still significant (p < .05) compared with the control group, whereas insulin treatment returned blood glucose and triglyceride to control levels. CONCLUSIONS: We demonstrate effective protection by insulin against T1DM-induced aortopathy in rats, which is associated with the inhibition of vascular injury biomarkers.

Subchronic administration of mitoxantrone and the influence of enzyme inhibitors on its induced cardiotoxicity in mice: role of NRF-2/CYP2E1.

OBJECTIVE: Mitoxantrone (MTX)- induced cardiotoxicity is a clinical concern that is limiting its use. The aim of this paper, therefore, was to investigate the subchronic administration of MTX plus nonspecific/specific inhibitors of CYP450/2E1, to assess the extent of oxidative-induced injury by measuring levels of oxidative cardiac and injury biomarkers in mice and to evaluate the effects of CYP2E1 on caspase 3 activity and nuclear factor erythroid 2-related factor-2 (NRF-2). MATERIALS AND METHODS: Mice (n = 32) were divided into four treatment groups of eight: control, MTX, MTX + 4-methlypyrazole (4MP) and MTX + disulfiram (Disf). After 6 weeks of treatments, blood and heart samples were collected. RESULTS: Liquid chromatography-mass spectrometry (LCMS) analysis of MTX-treated plasma samples revealed several metabolites with different retention times. Cardiac antioxidant enzymes and creatine kinase (CK) levels were not significantly different among the groups. However, cardiac troponin and caspase 3 activity were significantly raised, with increased CYP2E1 expressions and reduced NRF-2 expression. Tissue damage was observed in all the treatment groups, including MTX, leading to the conclusion that MTX-induced cardiotoxicity was mediated by CYP2E1 activity, which initiated caspase 3 production, and decreased NRF-2 expression. CONCLUSIONS: Therefore, agents that inhibit CPY2E1 expression might attenuate MTX-induced cardiotoxicity by increasing NRF-2 expression.

Production of Amidinyl Radicals via UV-Vis-Light Promoted Reduction of N-Arylthiophene-2-carboxamidoximes and Application to the Preparation of Some New N-Arylthiophene-2-carboxamidines.

A modern method for the preparation of some new N-arylthiophene-2-carboxamidines via amidinyl radicals generated using UV-vis-light promoting the reduction of N-arylthiophene-2-carboxamidoximes without any catalyst in a short amount of time, highly straight forward, and in an efficient manner is described. This method defeats the flaws of the conventional methods for the reduction of amidoxime derivatives to amidine derivatives, which require harsh conditions such as using a strong acid, high temperature, and expensive catalysts. Benzo[d]imidazoles, benzo[d]oxazoles, and amides can also be synthesized by applying this method. The photoproducts were analyzed by various spectroscopic and analytical techniques, including thin-layer chromatography, column chromatography, high-performance liquid chromatography, gas chromatography/mass spectrometry, IR, 1H NMR, 13C NMR, and MS. Notably, the chromatographic analyses proved that the best time for the production of N-arylthiophene-2-carboxamidines is 20 min. The reaction mechanism comprising pathways and intermediates was also suggested via the homolysis of N-O and C-N bonds.

Prevalence and types of genetic polymorphisms of CYP2C19 and their effects on platelet aggregation inhibition by clopidogrel.

OBJECTIVE: The current study was conducted to determine the distribution of genetic polymorphisms in CYP2C19 in Iraqi patients and their role in inter-individual variability of clopidogrel efficacy. PATIENTS AND METHODS: A prospective controlled study was done on 100 patients under high risk of cardiovascular diseases who started clopidogrel prophylactic therapy. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine the existence of the CYP2C19 gene mutation. Vasodilator-stimulated phosphoprotein (VASP) index baseline besides one-month post-therapy was analyzed by dual-color flow cytometry analysis. RESULTS: Eight gene mutations of CYP2C19 were found (*1/*1), (*1/*2), (*1/*3), (*1/*8), (*1/*17), (*2/*2), (*2/*4), and (*3/*3) with higher prevalent CYP2C19*1 gene. Homozygous CYP2C19*1 allele was shown to be the rapid metabolizer comparing to the heterozygous CYP2C19*1 allele, whereas, CYP2C19*2 and CYP2C19*3 were resistant alleles and were present in 28% of patients. The analysis of VASP phosphorylation produces accurate inter-individual response variability in platelets inhibition by antiplatelet drugs. CONCLUSIONS: In vitro gene analysis and VASP index improve the clinical outcome of a patient candidate to clopidogrel as prophylaxis in cardiovascular events.