Whey Protein Sodium-Caseinate as a Deliverable Vector for EGCG: In Vitro Optimization of Its Bioaccessibility, Bioavailability, and Bioactivity Mode of Actions.

Epigallocatechin gallate (EGCG), the principal catechin in green tea, exhibits diverse therapeutic properties. However, its clinical efficacy is hindered by poor stability and low bioavailability. This study investigated solid particle-in-oil-in-water (S/O/W) emulsions stabilized by whey protein isolate (WPI) and sodium caseinate (NaCas) as carriers to enhance the bioavailability and intestinal absorption of EGCG. Molecular docking revealed binding interactions between EGCG and these macromolecules. The WPI- and NaCas-stabilized emulsions exhibited high encapsulation efficiencies (>80%) and significantly enhanced the bioaccessibility of EGCG by 64% compared to free EGCG after simulated gastrointestinal digestion. Notably, the NaCas emulsion facilitated higher intestinal permeability of EGCG across Caco-2 monolayers, attributed to the strong intermolecular interactions between caseins and EGCG. Furthermore, the emulsions protected Caco-2 cells against oxidative stress by suppressing intracellular reactive oxygen species generation. These findings demonstrate the potential of WPI- and NaCas-stabilized emulsions as effective delivery systems to improve the bioavailability, stability, and bioactivity of polyphenols like EGCG, enabling their applications in functional foods and nutraceuticals.

Distinct leaflet-annular remodeling pattern in severe atrial functional mitral regurgitation: a three-dimensional echocardiography study.

BACKGROUND: Atrial functional mitral regurgitation (AFMR) is best described with normal left ventricular size and function, structurally normal mitral leaflets and dilated left atrium. Unlike the ventricular functional phenotype, changes in the annular geometry more than the tethering forces are the main culprit for mitral regurgitation. The aim of this study is to illuminate the leaflet-annular remodeling in patients with mitral regurgitation and atrial fibrillation (AF) using three-dimensional transesophageal echocardiography (3D TOE). RESULTS: Consecutive fifty patients with AFMR underwent transthoracic echocardiography and 3D TOE: 25 patients with AF and non-mild MR and 25 patients with AF and mild MR were studied. A special mitral valve analysis software was used to accurately assess the three unique pillars for MR: annular size, leaflets' geometry and tenting parameters. Compared to the mild MR group, non-mild MR group had long-standing AF of more than 1 year and larger left atrial volumes (51.83 ± 12.07 ml/m2 vs 33.68 ± 10.97 ml/m2, p < 0.001). No significant differences were noted in respect of tenting height, area and volume (13.06 ± 2.57 mm vs 11.43 ± 2.89 mm, p = 0.064, 3.58 ± 1.26 cm2 vs 2.80 ± 0.95 cm2, 0.081 and 6.70 ± 2.96 cm3 vs 5.04 ± 2.32 cm3, p = 0.081). Conversely, the non-mild MR group had larger annular area and perimeter (16.20 ± 3.90 cm2 vs 13.51 ± 3.85 cm2, p = 0.023 and 14.73 ± 1.72 cm vs 13.46 ± 1.79 cm, p = 0.033). Similarly, the non-mild MR group had larger anterior and posterior leaflets' areas (10.18 ± 4.02 cm2 vs 8.71 ± 3.08 cm2, p = 0.04 and 8.96 ± 2.60 cm2 vs 7.30 ± 2.17 cm2, p = 0.029). Correspondingly, more disproportionate leaflet-annular remodeling, as assessed by the ratio of total leaflets' area to the annular area, was noted in the non-mild MR as opposed to the mild MR group (1.22 ± 0.04 vs 1.26 ± 0.04, p = 0.008). CONCLUSIONS: Recently, AFMR has been recognized as a remarkable entity of secondary MR with unique mechanisms. Annular dilatation with disproportionate leaflet remodeling can validate the central regurgitation. However, the call for more parameters is being emphasized to characterize the suitable candidates for percutaneous interventions.

MXene@c-MWCNT Adhesive Silica Nanofiber Membranes Enhancing Electromagnetic Interference Shielding and Thermal Insulation Performance in Extreme Environments.

A lightweight flexible thermally stable composite is fabricated by combining silica nanofiber membranes (SNM) with MXene@c-MWCNT hybrid film. The flexible SNM with outstanding thermal insulation are prepared from tetraethyl orthosilicate hydrolysis and condensation by electrospinning and high-temperature calcination; the MXene@c-MWCNTx:y films are prepared by vacuum filtration technology. In particular, the SNM and MXene@c-MWCNT6:4 as one unit layer (SMC1) are bonded together with 5 wt% polyvinyl alcohol (PVA) solution, which exhibits low thermal conductivity (0.066 W m-1 K-1) and good electromagnetic interference (EMI) shielding performance (average EMI SET, 37.8 dB). With the increase in functional unit layer, the overall thermal insulation performance of the whole composite film (SMCx) remains stable, and EMI shielding performance is greatly improved, especially for SMC3 with three unit layers, the average EMI SET is as high as 55.4 dB. In addition, the organic combination of rigid SNM and tough MXene@c-MWCNT6:4 makes SMCx exhibit good mechanical tensile strength. Importantly, SMCx exhibit stable EMI shielding and excellent thermal insulation even in extreme heat and cold environment. Therefore, this work provides a novel design idea and important reference value for EMI shielding and thermal insulation components used in extreme environmental protection equipment in the future.

Coronary calcifications, the Achilles heel in coronary interventions.

Percutaneous coronary intervention in severely calcified coronaries has been associated with higher rates of procedural complications, including myocardial infarction and death in addition to increased frequency of coronary revascularization on an intermediate and long-term basis. The SYNTAX score, which is designed to assess the complexity of coronary artery disease and aids in choosing a revascularization method, allocates two points per lesion when there is heavy calcification present on fluoroscopy. With the advent of novel multimodality imaging technologies, the detection and evaluation of coronary calcifications improved significantly over the last decade. Several tools are now available for modifying calcified lesions including different types of dedicated balloons and atherectomy devices, which may create some degree of confusion regarding the suitable application of each instrument. The aim of this review is to cover this vital topic from different aspects. First, we tried to provide an overview on the pathophysiology and types of coronary calcification and its risk factors. Then, we outlined the available imaging modalities for the evaluation of calcified coronary lesions, highlighting the points of strength and weakness of each of them. A comprehensive discussion of calcium-modifying techniques was elaborated, summarizing their mechanism of action, pros and cons, and possible complications. Finally, an integrated algorithm was proposed for the best management of calcified coronary lesions.

Right Ventricular Response to Cardiac Resynchronization Therapy: A Three-Dimensional and Speckle Tracking Echocardiographic Study.

Cardiac resynchronization therapy (CRT) induces left ventricle reverse remodeling; however, its effects on right ventricular (RV) volumes and function were not well described. This study aimed to assess the effects of CRT on RV. Of 112 patients, 63 enrolled with a mean age of 62.77 ± 7.23 years, including 40 males (63.5%). All patients met criteria for CRT implantation and were followed at 3-month and 6-month intervals. Standard 2-dimensional/3-dimensional (3D) echocardiography and speckle-tracking analyses were conducted for assessment of LV and left atrium (LA). RV maximum diameters, tricuspid lateral annular systolic velocity, tricuspid annular plane systolic excursion, fractional area change, RV global (RV 4-chamber strain (RV4CSL), and RV free wall strain (RVFWSL), in addition to 3D echocardiographic assessment of RV, were done before CRT implantation and at follow-up visits. Mean follow-up period was 6.76 ± 1.25 months. A total of 48 patients (76.2%) were LV responders (LVR) whereas the rest were nonresponders (LVNR). Both groups had similar baseline characteristics, risk factors, device implantation, and programming values. Only LVR had significant reduction in RV basal diameter, together with significant improvement of RV systolic performance: systolic velocity, fractional area change, RV4CSL, RVFWSL, and 3D-derived RV volumes and ejection fraction, compared with baseline values. In addition, pulmonary arterial systolic pressure decreased in LVR with reduction of tricuspid regurgitation severity. LV response, percentage change of RV4CSL, LA end-systolic volume index, and LA emptying fraction at 3-month follow-up were the most independent predictors of RV response by multivariate analysis. Reduced left ventricular end-systolic volume >13.5% had 92.3% sensitivity and 81.8% specificity. In conclusion, CRT-induced RV reverse remodeling and improved RV-arterial coupling. These effects were associated with left side response to CRT.

Biochemical Profile and In Vitro Therapeutic Properties of Two Euhalophytes, Halocnemum strobilaceum Pall. and Suaeda fruticosa (L.) Forske., Grown in the Sabkha Ecosystem in the Algerian Sahara.

This study reports the biochemical profile and in vitro biological activities of the aerial part of two shrubs: Halocnemum strobilaceum and Suaeda fruticosa, a halophytes species native to saline habitats. The biomass was evaluated by determining its physiological properties and approximate composition. Hydro-methanolic extracts from Halocnemum strobilaceum and Suaeda fruticosa have been investigated for the inhibition of bacterial growth, the protection of proteins (albumin) from denaturation, and cytotoxicity to hepatocellular carcinomas (Huh-7 and HepG2). Their antioxidant activity was evaluated by five tests, including one that examined their ability to inhibit hydrogen peroxide (H2O2)-induced hemolysis. The profile of their phenolic compounds was also determined. These two euhalophytes had a high moisture content, high levels of photosynthetic pigments, elevated levels of ash and protein, low oxidative damage indices, MDA (Malondialdehyde) and proline, and low lipids levels. Their content was also characterized by a moderate acidity with good electrical conductivity. They contained abundant levels of phytochemicals and varied phenolic contents. Reverse phase high performance liquid chromatography (RP-HPLC) analysis revealed the presence of caffeic acid, p-coumaric acid, rutin, and quercetin in both plant extracts. On the pharmaceutical level, the two euhalophytes had anti-inflammatory, antibacterial, antioxidant, and cytotoxic properties, and therefore it was recommended to isolate and identify biologically active compounds from these plants and evaluate them in vivo.

Determination of Volatile Compounds of Mentha piperita and Lavandula multifida and Investigation of Their Antibacterial, Antioxidant, and Antidiabetic Properties.

Mentha piperita and Lavandula multifida are widely used in Moroccan traditional medicine for the treatment of diabetes and infectious diseases. The aims of this work were the determination of the chemical composition of Mentha piperita (MPEO) and Lavandula multifida (LMEO) essential oils and the evaluation of their antibacterial, antioxidant, and antidiabetic activities. The chemical composition was determined by GC-MS analysis. The antibacterial effects were evaluated against several bacterial strains using disc diffusion, MIC, and MBC methods. The antioxidant activity was evaluated in vitro using DPPH, H2O2, and xanthine oxidase, and the antidiabetic activity was estimated by the inhibitory effects of α-amylase, α-glucosidase, and lipase activities. GC-MS results showed that the main compounds of MPEO were menthone (29.24%), levomenthol (38.73%), and eucalyptol (6.75%). However, eucalyptol (28.11%), 2-bornanone (11.57%), endo-borneol (7.82%), and linalyl acetate (5.22%) are the major compounds of LMEO. The results exhibited important inhibitory effects against some bacterial strains with MIC = MBC = 0.39 mg/mL for MPEO against Staphylococcus aureus ATCC. However, LMEO exhibited remarkable antioxidant and antidiabetic activities compared to MPEO. Indeed, LMEO inhibited DPPH, H2O2, and xanthine oxidase with concentrations of 15.23, 21.52, and 8.89 µg/mL, respectively. Moreover, LMEO exhibited α-amylase and α-glucosidase at IC50 = 85.34 and IC50 = 59.36 µg/mL, respectively. The findings showed that both MPEO and LMEO exhibit promising biological properties. However, the application of these species or their main bioactive compounds requires further investigation.

UPLC/ESI-MS Phytochemical Screening of Deverra tortuosa Haematological and Histopathological Studies and Streptozotocin-Induced Diabetes in Rat.

Herbal plants represent a new source of hypoglycemic antidiabetic drugs; haematological and histopathological studies of methanol extract of Deverra tortuosa in streptozotocin-induced diabetic rats were investigated in vivo. A single intraperitoneal injection of 160 mg/kg bodyweights of streptozotocin was used to cause diabetes. Blood glucose levels were tested with an AccuCheck Advantage II glucometer and blood glucose test strips. After diabetes was confirmed, animals were orally treated with the extract, metformin, and insulin according to the experimental design. After extract therapy, histological alterations in the pancreas of diabetic rats were investigated. When compared to a control group, daily oral administration of D. tortuosa extract (300 mg/kg body weight) plus metformin (100 mg/kg) had a positive effect on blood glucose levels as well as showed an increased number of white blood cells (WBCs) and red blood cells (RBCs). The treatment with the extract for two weeks showed a positive impact on pancreatic histopathological changes in the groups with the diabetic rats. Phenolic fraction of the methanol extract was screened by the liquid chromatography-mass spectroscopy (LC-MS) method, which unveiled the existence of flavonoid compounds and phenolics as kaempferol, rutin, isorhamnetin-3-O-rutinoside, caffeic acid, and 4-hydroxybenzoic acid 4-O-glucoside. The results confirmed the use of the plant as an antidiabetic agent; the research recommended further studies on the plant to use the plant as an antidiabetic drug, where the plant extract also showed improvement in blood parameters.

Patient with Acute Coronary Syndrome in the Setting of an Extremely Rare form of Complex Congenital Anomalous Coronaries.

A single coronary artery is an exceedingly rare anomaly. Hereby, we present an unusual case of a young patient with an acute coronary syndrome who was found to have a single coronary artery originating from a single ostium in the right sinus of Valsalva with dual left anterior descending (LAD) arteries arising from the right coronary artery with two different anatomical courses, and additionally one of those LADs running a malignant intra-arterial course.

The protective effect of Indian Catechu methanolic extract against aluminum chloride-induced neurotoxicity, A rodent model of Alzheimer's disease.

Alzheimer's disease (AD) is the commonest neurodegenerative disorder with a wide array of manifestations, courses, and contributing causes. Despite being clinically characterized a long time ago; no treatment has been developed that could improve the pathology or slow down the disease manifestation- so far. Indian Catechu methanolic extract (ICME) has proved to have multiple beneficial effects that support its use in several disorders- especially those with complex etiology. In the present study, we evaluated the neuroprotective effect of ICME in a rat model of AD using Aluminum Chloride (AlCl3). The results showed that ICME could have a positive impact on the course of AD through its anticholinesterase effect and significant antioxidant effect which was reflected on the animals both on behavioral tests as well as hallmark pathological findings.

Effects of cardiac pacemakers on left ventricular volumes and function assessed by 3D echocardiography, Doppler method, and global longitudinal strain.

BACKGROUND: Many previous studies reported the negative effects of right ventricular (RV) pacing on the left ventricular (LV) structure and ejection fraction. Studying pacing hemodynamics is essential to understand these detrimental effects. In this study, we tried to understand RV pacing effects on LV volumes and function using advanced tools like 3D echo and global longitudinal strain (GLS). This was a prospective study of 175 consecutive patients (LVEF>50%) presented permanent pacing. Of 175 patients, only 50 patients met study criteria, divided into two groups (single or dual pacing). LV volumes and function were assessed by full-volume 3D echocardiography and GLS before pacing, at 1-week and 6-month post-pacing. Cardiac output (COP) was calculated by pulsed wave Doppler method and 3D echo. RESULTS: Doppler method results were similar to 3D echo in calculating SV and COP. At 1-week post pacing, both groups showed a significant decrease in SV due to a drop in EDV while ESV did not change significantly. Despite the drop in SV, there was a significant increase in cardiac output (COP) due to achieving higher heart rates post-pacing. There was a significant drop in EF and GLS in both groups. At 6 months, SV continued to decrease with a corresponding decrease in COP and LVEF. This drop in SV was due to a significant increase in ESV while EDV did not show a significant change at a 6-month follow-up. Also, the drop EF and GLS became more significant. There were no significant differences between both groups regarding the changes in LV volumes (EDV, ESV, SV), LVEF or GLS throughout the study (pre-pacing, at 1-week and 6-months post pacing). However, dual-chamber pacing group provided higher heart rates and as a result higher COP than the single-chamber group. CONCLUSIONS: RV pacing led to a significant drop in LV COP, ejection fraction (EF), and GLS over short- and long-term duration. Dual chamber pacing provided higher COP than a single chamber pacing. This was due to tracking the S. A node with pacing at higher heart rates not due to an increase in SV and preserving atrioventricular synchrony. Both Doppler method and 3D echo can be used to calculate SV and COP.

Effect of habitat variations on the chemical composition, antioxidant, and antimicrobial activities of Achillea fragrantissima (Forssk) Sch. Bip.

Achilea fragmentisma plant is widely distributed along northern regions of Saudi Arabia with various traditional medical uses. The plant was collected from Tabuk and Arar regions to study the effect of the variation in habitat on the chemical compositions, antimicrobial and antioxidant activities of the plant. The results showed significant differences between the two studied region regarding the parameters of the weather in years from 2010-2016.The antioxidant and antimicrobial of the plant showed significant variation in two habitats. Plant collected from Arar showed high antioxidant activity with IC50 (0.21 ± 0.01 g/L) by DPPH radical scavenging methods, and good antibacterial activity with gram-positive bacteria (Staphylococcus epidermidis, Bacillus cereus and Staphylococccus aureus clinical isolate), antibacterial activity ranging between high to no activity (between 14.5 ± 0.5-6.0 ± 0.0 mm zone of inhibition), On the other side the tested plant extracts showed no effect on, all gram-negative bacteria. GC/MS data showed marked variation in chemical compositions of both phenolic and alkaloid compounds in plants collected from both regions. Phenolic compounds were accumulated with higher amounts(Ferulic acid, Eugenol and Salicylic acid ester) in Arar region, while the alkaloid fractions (Ethyl isoallocholate, Pterin 6-carboxylic-acid and kadain) showed higher concentrations in plants collected from Tabuk region. The results reflect the variation in of weather parameter, affect on chemical compositions and biological activities of the plant in two studied regions.

Predictors of pacing induced left ventricular dysfunction and cardiomyopathy assessed by three-dimensional echocardiography and speckle tracking strain.

BACKGROUND: Long-term RV pacing leads to ventricular dyssynchrony, in the form of LBBB-like morphology, with subsequent detrimental effects on LV structure and function. Three-dimensional echocardiography allowed early detection of volumetric changes associated with PICMP and provided more accurate assessment of mechanical dyssynchrony. Speckle tracking strain is able to identify LV dysfunction even before any reduction in LVEF. Our aim was to study pacing effects on LV function and hemodynamics using 3D echo and speckle tracking strain. RESULTS: This was a prospective study of 175 consecutive patients without structural heart disease (LVEF > 50%) presented for permanent pacing. Full-volume 3D echocardiography done before implantation, 1 week, and 6 months together with GLS. Patients were followed for 6 months to detect incidence of PIVD (defined as reduction in LVEF > 10% but still above 50%) and PICMP (defined as decrease in LVEF by 10% from baseline in absence of other known causes of cardiomyopathy resulting in EF< 50%). PIVD and PICMP predictors and risk factors were analyzed. Only 50 patients met study criteria. Twenty-five (50%) patients developed LV systolic dysfunction; of these, 19 (38%) developed PIVD and 6 (12%) developed PICMP. Pre-implantation GLS was significantly lower in the 6 patients who subsequently developed PICMP, compared to those who developed PIVD and the preserved EF group (mean GLS - 15.50 vs. - 21.0, - 20.0 respectively; p = 0.005, 0.033, respectively). At 1 week, GLS was significantly lower in the 25 patients who subsequently developed PIVD, compared to those who did not (GLS - 13.0 vs. - 18.0, respectively; p = 0.002). A reduction of baseline GLS by 15% or more at 1 week was associated with the development of PIVD and PICMP (p = < 0.001). A wider native QRS complex was associated with PIVD and PICMP (p = 0.008, 0.018, respectively). The other predictors were found non-significant. CONCLUSION: PICMP may be more common than previously reported and it may occur shortly after implantation. Pre-implantation GLS is a sensitive parameter for PICMP. One-week GLS, pre-implantation QRS complex width are early predictors for PICMP and PIVD before any reduction in EF.

Medicinal Applications of Cannabinoids Extracted from Cannabis sativa (L.): A New Route in the Fight Against COVID-19?

Cannabis sativa is a well-known plant that has been recognized for its benefits since ancient times by several medicinal systems, including those of China, India, Greece, and Egypt. Although C. sativa is one of the most investigated medicinal plants in the world, it faces some of the greatest controversies surrounding its legalization and use as a medication. C. sativa contains several hundred phytoconstituents, including the infamous "cannabinoids". It is necessary to properly understand the medicinal importance of these phytochemicals and spread awareness among the countries where cannabis is still facing legal obstacles. The current review focuses on the most recent literature pertaining to various applications of cannabinoids, with a special focus on the medicinal aspect of these phytochemicals. Peer-reviewed articles focusing on the importance of cannabis and cannabinoids are the target of this review. Articles were selected based on the relevance to the general scope of the work, i.e., application of cannabinoids. Cannabinoids can truly be regarded as wonder drugs, considering their immense diversity of usage. Unfortunately, however, many of the mares have never been researched biologically or pharmacologically due to their low yield in the plant. However, the approval of some cannabinoids by the FDA (along with other recognized national medical health systems) has opened the horizon for the use of these natural drugs in medicines such as Epidiolex® (cannabidiol, used for the treatment of severe forms of epilepsy) and Sativex®(Δ9-tetrahydrocannabinol and cannabidiol, used for the treatment of spasticity caused by multiple sclerosis). Many pharmacological properties of C. sativa are attributed to cannabidiol (CBD), a non-psychoactive component, along with Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive component. This review addresses the most important applications or current utilization of cannabinoids in a variety of treatments such as chronic pain, cancer, emesis, anorexia, irritable bowel syndrome, communicable diseases, glaucoma, and central nervous system disorders. The biosynthetic pathway of cannabinoids is also discussed. In short, cannabis has a myriad of bioactive compounds that have the potential to increase the list of approved cannabinoids suitable for therapy.

Chemical composition, antifungal and antiproliferative activities of essential oils from Thymus numidicus L.

In this study, Thymus numidicus Poir. plant material was collected from two different locations in north-western Tunisia and the aerial parts essential oils (EOs) were extracted via hydro-distillation. Gas chromatography coupled to mass spectrometry (GC-MS) and flame ionisation detection (GC-FID) were used for the qualitative analysis and quantification of the volatile constituents. Thymol (50.1-52.8%) was identified as the main compound of both EOs. To evaluate the potential application of the EOs as antifungal agents, the in vitro inhibitory effects were tested against six fungal strains; a strong antifungal activity of one sample was observed (MIC = 40-400 µg/mL). The in vitro antiproliferative activity was investigated on two human cancer cell lines, i.e. the colonic (HCT116) and breast adenocarcinoma (MCF7) using the colourimetric MTT assay. Again, the same sample demonstrated to possess good antiproliferative activity against both cancer cell lines, with IC50 values of 26.9 and 11.7 µg/mL, respectively.

DFT calculations and POM analyses of cytotoxicity of some flavonoids from aerial parts of Cupressus sempervirens: Docking and identification of pharmacophore sites.

Two known polyphenols named apigenin 7-O-ß-d-glucopyranoside (S1) and querctine-3-O-glucoside (S2), along with another two new compounds apigenin 4'-geranyl-8-glucopyranosyl-7-O-α-glucopyranoside (S3) and apigenin 4'-pernyl-8-glucopyranosyl -7-O-α-glucopyranoside (S4), were isolated from the leaves of Cupressus sempervirens. Structure elucidation of the isolated polyphenols was established on the basis of detailed spectroscopic analysis like 1D and 2D NMR analyses including 1H NMR, 13C NMR, COSY, DEPT, HMQC, UV, and Electron Spray Ionization Mass Spectroscopy (ESI-MS). Density Functional Theory (DFT) of computational, Petra/Osiris/Molinspiration (POM), and docking analyses methods were applied in the structural validation of new isolated compounds. The isolated compounds S1-S4 showed significant cytotoxicity against human hepatocellular liver carcinoma HepG2 cells, MCF-7, HC116 and A549.

Cardiac chloroma or cardiac myeloid sarcoma: Case Report.

Chloroma or myeloid sarcoma is rare extramedullary tumor composed of immature myeloid cells that may occur in association with or during or even before the course of adult myelodysplastic or myeloproliferative diseases. It may involve different organs including the orbit, skin, lymph nodes, bone, gastrointestinal tract, breast, central nervous system, and lung. Cardiac involvement with MS is an exceedingly rare finding. We report a very rare case of left ventricular cardiac chloroma accidentally discovered by transthoracic echocardiography (TTE) and confirmed by cardiac magnetic resonance (CMR) in an old aged male patient with acute myeloid leukemia (AML) French-American-British (FAB)-class M5. Unfortunately, shortly after a prompt start of AML palliative chemotherapy protocols, the patient died due to massive intracranial hemorrhage (ICH).

Silver nanoparticles testicular toxicity in rat.

To evaluate the potential testicular toxicity induced by silver nanoparticles (AgNPs) in Sprague Dawley rate. The protocol study was designed as follows: G1: 30 adult male rats were kept as control. G2: 30 adult male rats were administered 5.36 mg/kg of AgNPs orally, twice weekly for six months. G3: 30 adult male rats were administered 13.4 mg/kg of AgNPs orally, twice weekly for six months. The results of hormonal assay revealed that a significant decrease in testosterone level while a significant increase in LH level was obtained. The testicular homogenate showed a significant decrease in SOD activity accompanied by a significant increase in MDA level in both G2 and G3 in comparison with the control in a dose-response relationship. Sperm viability indicates a significant decrease in rats in G2 and G3 groups. A significant decrease in DNA chromatin integrity % was obtained in rats of G3 in comparison with G2 and control. The semithin and TEM sections of the testis of G2 and G3 groups showed Sertoli cells have vacuolations with a disturbance in the arrangement and the staining affinity of spermatogenic cells. The spermatogonia appeared with a moderate electron density of the nucleus and cytoplasm. The acrosome and its cap become oval and light electron dens of spermatid cells.

Mancozeb impaired male fertility in rabbits with trials of glutathione detoxification.

The study aims to evaluate the potential reproductive toxicity induced by mancozeb fungicide in male rabbits and to examine the ameliorative effect of glutathione (GSH), a non-enzymatic antioxidant, against mancozeb reproductive toxicity. Mancozeb is a member of the dithiocarbamates group currently in use in the management of fungal diseases of plants. To achieve these aims, mature male White New-Zealand rabbits of 4-5 months old were randomly assigned to four groups of 9 animals each: control, mancozeb only, mancozeb and GSH, and GSH only. This study discovered a significant reduction in serum FSH, LH, testosterone and testicular LDH, ACP, and ALP levels in the groups of mancozeb-treated rabbits compared with control. The mancozeb-treated groups also showed significant losses in sperm viability, along with a significant increase in the number of abnormal sperms. Finally, an upregulation in steroidogenic 3ß-HSD enzyme activity was noted in mancozeb-treated rabbits. Histopathological inspection of the testicles established disruption of the germinal epithelium with vacuolization of Leydig cells and reduced spermatogenic cells. GSH co-administration increased serum concentrations of FSH, LH, testosterone, and levels of the testicular enzymes: LDH, ACP, and ALP. Improved steroidogenesis was indicated in this group by a significant improvement in the testicular 3ß-HSD enzyme, by a significant increase in sperm viability, and by a significant decrease in the number of abnormal sperms. The findings of this study suggest that mancozeb exposure has anti-spermatogenic and anti-steroidogenic adverse effects in rabbits and administration of GSH may alleviate the reproductive toxicity.

Co-administration of glutathione alleviates the toxic effects of 2,3,7,8 TCDF on the DNA integrity of sperm and in the testes of mice.

This study aimed to investigate the toxic impact prompted in the testes of adult mice exposed to 2,3,7,8-tetrachlorodibenzofuran (TCDF). Four groups of 12 mice each were used in the present study. Group 1 mice were kept as control and administered corn oil only. Group 2 animals were given glutathione (GSH) in a dose of 100 mg/kg body weight by oral gavage twice a week. Group 3 was given TCDF orally twice per week, in a dose of 0.5 µg/kg body weight for 8 weeks. Group 4 was administered GSH orally in a dosage of 100 mg/kg body weight plus TCDF twice a week for 8 weeks. Animals were sacrificed after 2, 4, and 8 weeks of exposure, serum samples were collected for estimation of testosterone hormone, the testes were dissected and one part was used for estimation of superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), and 3ß-hydroxysteroid dehydrogenase. Another portion of the testis was kept in formalin for histopathological examination. The results showed that the activities of SOD were decreased while the levels of lipid peroxidation MDA were increased in the testicular tissues of the exposed mice. The serum testosterone level and the steroidogenic enzyme 3ß-hydroxysteroid dehydrogenase activity of testicular homogenate were essentially decreased in TCDF-treated mice. A significant increment in the testicular LDH activity in testicular tissues was recorded in mice exposed to TCDF. The percentage of DNA chromatin disintegration was significantly increased in TCDF-treated mice. Histopathological changes were recorded in TCDF-exposed group as degenerative changes of the seminiferous tubules with formation of spermatid giant cells at 2 weeks in addition to exhaustion of germinal epithelium and detachment of the germ cells from the basal lamina at 4 and 8 weeks. Co-administration of GSH could reestablish MDA and LDH levels besides reduction in percentage of sperm DNA damage and improvement of the testicular tissue architecture.