P-gp inhibition and enhanced oral bioavailability of amikacin Sulfate: A novel approach using Thiolated Chito-PEGylated Lipidic Hybrids.

This study aimed to develop oral lipidic hybrids of amikacin sulfate (AMK), incorporating thiolated chitosan as a P-glycoprotein (P-gp) inhibitor to enhance intestinal absorptivity and bioavailability. Three formulations were designed: PEGylated Liposomes, Chitosan-functionalized PEGylated (Chito-PEGylated) Lipidic Hybrids, and Thiolated Chito-PEGylated Lipidic Hybrids. The physical characteristics of nanovesicles were assessed. Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted to evaluate the formulations' potential to enhance AMK intestinal permeability. In-vivo pharmacokinetic studies in rats and histological/biochemical investigations assessed the safety profile and oral bioavailability. The AMK-loaded Thiolated Chito-PEGylated Lipidic Hybrids exhibited favorable physical characteristics, higher ex-vivo permeation parameters, and verified P-gp inhibition via CLSM. They demonstrated heightened oral bioavailability (68.62% absolute bioavailability) and a sufficient safety profile. Relative bioavailability was significantly higher (1556.3% and 448.79%) compared to PEGylated Liposomes and Chito-PEGylated Lipidic Hybrids, respectively, indicating remarkable oral AMK delivery with fewer doses, reduced side effects, and enhanced patient compliance.

Flawless polyaniline coating for preservation and corrosion protection of ancient steel spearheads: an archaeological study from military museum, Al-Qala, Egypt.

The purpose of this research was to examine the viability of applying a flawless polyaniline coating on steel spearheads to preserve them and protect them from corrosion. The spearpoints, thought to be archaeologically significant, were acquired from the Military Museum in Al-Qala, Egypt. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy were used to characterize the spearheads chemical composition and microstructure (EDX). The spearheads were determined to be constructed of steel and to have a coating of ferric oxide and other corrosion products on their exteriors. After that, a flawless polyaniline coating was electrochemically deposited onto the spearpoints in a way that was both quick and cheap. Many types of corrosion tests, such as electrochemical impedance spectroscopy and potentiodynamic polarization (PDP) readings, were used to determine the coating's effectiveness. The steel spearheads' findings revealed a significant improvement in their resistance to corrosion after being coated with flawless polyaniline. The coating served as a barrier, blocking out water and other corrosive substances and slowing the buildup of corrosion byproducts on the spearpoints. In conclusion, our research shows that a flawless polyaniline coating may be an effective anti-corrosion treatment for ancient steel artifacts. The approach is straightforward, cheap, and readily scalable for massive conservation efforts.

Renal arterial resistive index versus novel biomarkers for the early prediction of sepsis-associated acute kidney injury.

Acute kidney injury (AKI) is a critical complication of sepsis. There is a continuous need to identify and validate biomarkers for early detection. Serum and urinary biomarkers have been investigated, such as neutrophil gelatinase associated lipocalin (NGAL) and cystatin C (Cys C), but their reliability in the intensive care unit (ICU) remains unknown. Renal hemodynamics can be investigated by measuring the renal resistive index (RRI). This study aimed to compare the performance of RRI, serum NGAL (sNGAL), urinary NGAL (uNGAL), and serum Cys C levels as early predictors of the diagnosis and persistence of sepsis-associated AKI. A total of 166 adult patients with sepsis syndrome were enrolled immediately after ICU admission. Biomarkers were measured directly (T1) and on day 3 (T3). RRI was measured directly (T1) and 24 h later (T2). Patients were categorized (according to the occurrence and persistence of AKI within the first 7 days) into three groups: no AKI, transient AKI, and persistent AKI. The incidence rate of sepsis-associated AKI was 60.2%. Sixty-six patients were categorized as in the no AKI group, while another 61 were in transient AKI and only 39 were in persistent AKI. The RRI value (T1 ≥ 0.72) was the best tool for predicting AKI diagnosis (area under the receiver operating characteristic curve, AUROC = 0.905). Cys C (T1 ≥ 15.1 mg/l) was the best tool to predict the persistence of AKI (AUROC = 0.977). RRI (T1) was the best predictive tool for sepsis-associated AKI, while Cys C was the best predictor of its persistence and 28-day mortality.

The Versatility of the Lateral-based Mammary Flap as an "Auto-implant" for Enhancing Breast Mound for Patients Undergoing Primary Mastopexy.

Background: The demand for augmentation-mastopexy surgery without using implants has significantly increased over the years. Fat transfer offers an alternative method, but some patients do not favor this procedure either. The purpose of this study was to evaluate the versatility of using a lateral-based mammary flap as an "auto-implant" for enhancing the breast mound for patients undergoing primary mastopexy. Method: This retrospective study was performed between February 2016 and April 2019, including 36 female patients (72 breasts). Our technique involves using the inferior breast tissue by elevating the lateral-based dermoglandular flap that was moved cranially with a 90 degree rotation in a conical shape within the created pocket to refill the superior and central mound. Result: The mean nipple projection was 11.2 after 36 months postoperative compared with 5.2 before surgery. The mean ± SD of pre- and postoperative measurements for the lower pole zone were 80.2 ± 10.5 and 50.1 ± 6.4, and those for the upper pole zone were 40.3 ± 9.5 and 63.9 ± 6.5, respectively. The distance of breast mound elevation after the surgical procedure ranged from 5.30 to 9.55 cm, with a mean of 7.90 cm. Conclusions: The lateral-based mammary flap acts like an implant that helps shape and augment the breast, enhances the mammary projection, and restores the breast contour without requiring a synthetic implant or fat grafting. It is a reliable technique with high patient satisfaction but is unsuitable for patients with insufficient breast volume.

Mycoplasmosis in Poultry: An Evaluation of Diagnostic Schemes and Molecular Analysis of Egyptian Mycoplasma gallisepticum Strains.

Infections with Mycoplasma gallisepticum (MG) in poultry are associated with a wide range of disease conditions, including those affecting the respiratory and reproductive systems. The purpose of this study was to endorse the more sensitive diagnostic scheme for MG infection and identify the best molecular marker for MG phylogenetic analysis using six housekeeping genes: mgc2, mraW, atpG, ugpA, DUF31196, and lgT. For these purposes, 55 poultry flocks of different species were screened using either qRT-PCR or PCR techniques analogous to conventional culturing from non-cultured and cultured swabs on PPLO broth. The rate of MG positivity was the highest when using qRT-PCR from cultured broth (89.0%) and the lowest when using conventional culturing (34.5%). Compared to qRT-PCR from broth, statistical analysis using the Roc curve in MedCalc statistical software showed that the PCR schemes (qRT-PCR from swabs and PCR from swabs and broth) performed better than conventional culturing in terms of sensitivity, accuracy, and area under the curve (AUC), suggesting that they may be more reliable schemes. Further support was added by Cohen's kappa test, showing moderate agreement between the molecular approaches. Among the six screened genes, mgc2 and mraW had the highest detection rates (69% and 65.4%, respectively). The comparative phylogenetic analysis revealed that mgc2 or atpG gene sequences distinguished MG isolates into different clades with high discriminatory power.

Evaluation and development of diagnostic tools for rapid detection of Riemerella anatipestifer and Pasteurella multocida in ducks.

Objectives: Ducks suffer a huge economic loss as a result of infections with Pasteurella multocida and Riemerella anatipestifer, which cause high morbidity and mortality. Because these pathogens induce similar clinical symptoms when coinfections occur, it is very difficult to differentiate between them based just on clinical signs. Hence, these major pathogens must be quickly and accurately detected. Materials and Methods: A total of 104 birds ranging from 2 days to 4 weeks old were collected from Egyptian farms, and the outcomes were compared statistically. Conventional cultural identification procedures and a direct multiplex polymerase chain reaction assay were utilized to recognize both pathogens in a single tube reaction simultaneously. Then, the obtained isolates were characterized phenotypically and genotypically. Results: Clinical signs appear at 2-4 weeks of age with respiratory distress (dyspnea), white fluid feces, and stunting. The scrutinized data demonstrated a significantly higher detection rate by PCR directly compared to classical culture procedures. Pasteurella multocida was detected only by PCR. The disc diffusion technique against ten antibiotics showed absolute susceptibilities to amikacin, doxycycline, and florfenicol. High levels of beta-lactam resistance were observed. Riemerella anatipestifer isolates were screened for pathogenicity and plasmid-borne blaTEM genes. All six isolates harbored five virulence genes: aspC, RA46, m28, pstS, and Nlp/P60. Moreover, blaTEM was identified into four isolates and deposited to GenBank with accession numbers OP347083, OP347084, OP347085, and OP347086. Conclusion: These results suggest advanced PCR assays can be applied to the field for rapid and valuable diagnosis of two significant pathogens and focus on the worth of ducks in the propagation of transferable antibiotic resistance genes into the environment.

Influence of Surface-Modification via PEGylation or Chitosanization of Lipidic Nanocarriers on In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Apixaban.

Nanostructured lipid carriers (NLCs) have been proven to significantly improve the bioavailability and efficacy of many drugs; however, they still have many limitations. These limitations could hinder their potential for enhancing the bioavailability of poorly water-soluble drugs and, therefore, require further amendments. From this perspective, we have investigated how the chitosanization and PEGylation of NLCs affected their ability to function as a delivery system for apixaban (APX). These surface modifications could enhance the ability of NLCs to improve the bioavailability and pharmacodynamic activity of the loaded drug. In vitro and in vivo studies were carried out to examine APX-loaded NLCs, chitosan-modified NLCs, and PEGylated NLCs. The three nanoarchitectures displayed a Higuchi-diffusion release pattern in vitro, in addition to having their vesicular outline proven via electron microscopy. PEGylated and chitosanized NLCs retained good stability over 3 months, versus the nonPEGylated and nonchitosanized NLCs. Interestingly, APX-loaded chitosan-modified NLCs displayed better stability than the APX-loaded PEGylated NLCs, in terms of mean vesicle size after 90 days. On the other hand, the absorption profile of APX (AUC0-inf) in rats pretreated with APX-loaded PEGylated NLCs (108.59 µg·mL-1·h-1) was significantly higher than the AUC0-inf of APX in rats pretreated with APX-loaded chitosan-modified NLCs (93.397 µg·mL-1·h-1), and both were also significantly higher than AUC0-inf of APX-Loaded NLCs (55.435 µg·mL-1·h-1). Chitosan-coated NLCs enhanced APX anticoagulant activity with increased prothrombin time and activated partial thromboplastin time by 1.6- and 1.55-folds, respectively, compared to unmodified NLCs, and by 1.23- and 1.37-folds, respectively, compared to PEGylated NLCs. The PEGylation and chitosanization of NLCs enhanced the bioavailability and anticoagulant activity of APX over the nonmodified NLCs; this highlighted the importance of both approaches.

Outcomes of family-centred auditory and tactile stimulation implementation on traumatic brain injured patients.

AIM: To determine the outcomes of Family-centred Auditory and Tactile Stimulation Implementation on Traumatic Brain Injured Patients in Egypt. BACKGROUND: Family engagement in the care of their relatives in the Intensive care units is limited due to patients' life-threatening conditions, in addition to the use of high technology in these settings. Auditory and tactile sensory stimulations are among the diverse sensory stimulations that have received more attention in brain injured patients than other senses as being considered safe, and effective measures. DESIGN: A Quasi-experimental design was used to test the hypotheses of this study. METHODS: A convenience sample of 60 adult patients suffering from Traumatic Brain Injury and admitted to the intensive care units of two University Hospitals in Egypt was included in the study. Patients were assigned into two equal groups: control and study groups (30 patients each). The auditory and tactile stimulations were provided by trained family members, once daily for 2 weeks for the study group. Whereas routine communication was provided by the family of traumatic brain injured patients in the ICU for the control group. Two tools were used for data collection; tool one, the "Glasgow Coma Scale" to assess patient's level of consciousness, and tool two the "Physiological Adverse Events Assessment" to monitor patients for the occurrence of physiological adverse events. DATA COLLECTION: January to October 2019. RESULTS: The implementation of an organized auditory and tactile stimulation by trained family members is associated with highly statistically significant positive effects . Patients in the study group showed a higher mean of consciousness, lower incidence rate of physiological adverse events, and a lower mean duration of ICU stay. CONCLUSIONS: Implementation of an organized auditory and tactile stimulation by trained family members enhanced the consciousness level of comatose Traumatic Brain Injured patients, decreased the occurrence of physiological adverse events, and ICU length of stay. Thus, it is recommended for use in the daily routine nursing care of comatose Traumatic Brain Injured patients. RELEVANCE TO CLINICAL PRACTICE: This study gives a deeper understanding of how family engagement in the care of their critically ill relative enhances their recovery and improve their level of consciousness.

Effect of nanovesicular surface-functionalization via chitosan and/or PEGylation on cytotoxicity of tamoxifen in induced-breast cancer model.

AIMS: The effect of surface-modification of Tamoxifen (Tam)-loaded-niosomes on drug cytotoxicity and bio-distribution, via functionalization with chitosan and/or PEGylation, was investigated. MATERIALS AND METHODS: Tam-loaded hybrid-nanocarriers (Tam-loaded niosomes, chitosomes, PEGylated niosomes, and PEGylated chitosomes) were formulated and characterized. KEY FINDINGS: Chitosanization with/without PEGylation proved to selectively enhance Tam-release at the cancerous-acidic micromilieu. Cytotoxic activity study showed that Tam-loaded PEGylated niosomes had a lower IC50 value on MCF-7 cell line (0.39, 0.35, and 0.27 times) than Tam-loaded PEGylated chitosomes, Tam-loaded niosomes, and Tam-loaded chitosomes, respectively. Cell cycle analysis showed that PEGylation and/or Chitosanization significantly impact Tam efficiency in inducing apoptosis, with a preferential influence of PEGylation over chitosanization. The assay of Annexin-V/PI double staining revealed that chitosanized-nanocarriers had a significant role in increasing the incidence of apoptosis over necrosis. Besides, PEGylated-nanocarriers increased apoptosis, as well as total death and necrosis percentages more than what was shown from free Tam. Moreover, the average changes in both Bax/Bcl-2 ratio and Caspase 9 were best improved in cells treated by Tam-loaded PEGylated niosomes over all other formulations. The in-vivo study involving DMBA-induced-breast cancer rats revealed that PEGylation made the highest tumor-growth inhibition (84.9 %) and breast tumor selectivity, while chitosanization had a lower accumulation tendency in the blood (62.3 ng/ml) and liver tissues (103.67 ng/ml). The histopathological specimens from the group treated with Tam-loaded PEGylated niosomes showed the best improvement over other formulations. SIGNIFICANCE: All these results concluded the crucial effect of both PEGylation and chitosan-functionalization of Tam-loaded niosomes in enhancing effectiveness, targetability, and safety.

Early assessment of aspiration risk in acute stroke by fiberoptic endoscopy in critically ill patients.

BACKGROUND: Fiberoptic endoscopic evaluation of swallowing (FEES) has been recommended to assess aspiration in stroke. This study aimed to determine the diagnostic and prognostic roles of FEES in the early assessment of aspiration, intensive care unit (ICU) stay and mortality in acute stroke patients. METHODS: Fifty-two patients with acute stroke admitted to the Alexandria Main University Hospital were included. Complete examinations and assessment of aspiration using the 8-point penetration-aspiration scale (PAS) with FEES protocol were performed. RESULTS: The patients were classified into three groups: normal with no or low risk of aspiration (n=15, 27.3%; PAS level 1), low to moderate risk (n=8, 14.5%; PAS level 2-4), and high risk (n=32, 58.2%; PAS ≥5). There was high incidence of aspiration pneumonia, prolonged ICU stay, and mortality in both moderate- and high-risk groups (P=0.001, P<0.001, and P<0.001, respectively). The PAS score predicted aspiration pneumonia (hospital-acquired pneumonia) with sensitivity and specificity of 80.0% and 76.0%, respectively (negative predictive value [NPV], 76.0; positive predictive value [PPV], 80.0; 95% confidence interval [CI], 0.706-0.940) and mortality with sensitivity and specificity of 88.46% and 68.97% (NPV, 87.0; PPV, 71.9; 95% CI, 0.749-0.951). The PAS score could predict the length of ICU stay with sensitivity and specificity of 70.21% and 87.50, respectively (NPV, 33.3; PPV, 97.1; 95% CI, 0.605-0.906). CONCLUSIONS: The standard FEES protocol using PAS score is a useful tool to assess aspiration in acute stroke patients and could be used to predict length of ICU stay and mortality.

Role of ascorbic acid infusion in critically ill patients with transfusion-related acute lung injury.

INTRODUCTION: In critically ill patients, transfusion-related acute lung injury (TRALI) remains the leading cause of transfusion-related fatalities in critical care settings and is associated with inflammation and oxidative stress state. Recent research raised the potential efficacy of high-dose intravenous ascorbic acid (VC) in critically ill patients. OBJECTIVE: The aim of this trial was to investigate the effect of high-dose intravenous VC as a targeted therapy for TRALI in terms of serum proinflammatory (interleukin [IL]-8, IL-1ß, C-reactive protein), anti-inflammatory (IL-10), oxidative stress (superoxide dismutase, malondialdehyde) markers, and plasma VC levels. Secondary outcomes were oxygenation (PaO2 /FiO2 ratio), vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-day mortality and 28-day mortality. METHODS: Eighty critically ill patients with TRALI (n = 80) were randomized to receive 2.5 g/6 h intravenous vitamin C for 96 hours (ASTRALI group) or placebo. Patients were followed up to measure the outcomes initially (T0) and at the end of treatment (T96). RESULTS: When compared to the control group, the ASTRALI group at T96 showed significantly higher median of IL-10 (31.6 ± 25.8 vs 17.7 ± 12.0 pg/mL, P < .0001) levels and superoxide dismutase (12 876 ± 4627 U/L vs 5895 ± 6632 U/L, P < .0001) activities, and lower median C-reactive protein (76 ± 50 vs 89 ± 56 mg/L, P = .033), IL-8 (11.8 ± 7.3 vs 35.5 ± 19.8 pg/mL, P < .0001) and malondialdehyde (0.197 ± 0.034 vs 0.234 ± 0.074 µM/L, P = .002) levels. CONCLUSION: High-dose ascorbic acid was associated with significantly reduced oxidative stress, reduced pro-inflammatory markers except IL-1ß, elevated anti-inflammatory marker and elevated plasma VC levels.

Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity.

Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to increase its bioavailability and effectiveness. As solid lipid, liquid lipid, hydrophilic, and lipophilic stabilizers, stearic acid, oleic acid, Tween 80, and lecithin were used, respectively. Utilizing Box-Behnken design, the effects of three factors on NLC particle size (Y1), zeta potential (Y2), and entrapment efficiency percent (Y3) were examined and optimized. The optimized formula was prepared, characterized, morphologically studied, and pharmacokinetically and pharmacodynamically assessed. The observed responses of the optimized Apx formula were 315.2 nm, -43.4 mV, and 89.84% for Y1, Y2, and Y3, respectively. Electron microscopy revealed the homogenous spherical shape of the NLC particles. The in vivo pharmacokinetic study conducted in male Wistar rats displayed an increase in AUC and Cmax by 8 and 2.67 folds, respectively, compared to oral Apx suspension. Moreover, the half-life was increased by 1.94 folds, and clearance was diminished by about 8 folds, which makes the NLC formula a promising sustained release system. Interestingly, the pharmacodynamic results displayed the superior effect of the optimized formula over the drug suspension with prolongation in the cuticle bleeding time. Moreover, both prothrombin time and activated partial thromboplastin time are significantly increased. So, incorporating Apx in an NLC formula significantly enhanced its oral bioavailability and pharmacodynamic activity.

Cholesterol-Based Nanovesicles Enhance the In Vitro Cytotoxicity, Ex Vivo Intestinal Absorption, and In Vivo Bioavailability of Flutamide.

Critical adverse effects and frequent administration, three times per day, limit the use of flutamide (FLT) as a chemotherapeutic agent in the treatment of prostate cancer. Therefore, our research aimed to develop new cholesterol-based nanovesicles for delivering FLT to malignant cells in an endeavor to maximize its therapeutic efficacy and minimize undesired adverse effects. Draper-Lin small composite design was used to optimize the critical quality attributes of FLT-loaded niosomes and ensure the desired product quality. The influence of the selected four independent variables on mean particle size (Y1), zeta potential (Y2), drug entrapment efficiency (Y3), and the cumulative drug release after 24 h (Y4) was examined. The optimized nanovesicles were assessed for their in vitro cytotoxicity, ex-vivo absorption via freshly excised rabbit intestine as well as in vivo pharmacokinetics on male rats. TEM confirmed nanovescicles' spherical shape with bilayer structure. Values of dependent variables were 748.6 nm, -48.60 mV, 72.8% and 72.2% for Y1, Y2, Y3 and Y4, respectively. The optimized FLT-loaded niosomes exerted high cytotoxic efficacy against human prostate cancer cell line (PC-3) with an IC50 value of 0.64 ± 0.04 µg/mL whilst, it was 1.88 ± 0.16 µg/mL for free FLT. Moreover, the IC50 values on breast cancer cell line (MCF-7) were 0.27 ± 0.07 µg/mL and 4.07 ± 0.74 µg/mL for FLT-loaded niosomes and free FLT, respectively. The permeation of the optimized FLT-loaded niosomes through the rabbit intestine showed an enhancement ratio of about 1.5 times that of the free FLT suspension. In vivo pharmacokinetic study displayed an improvement in oral bioavailability of the optimized niosomal formulation with AUC and Cmax values of 741.583 ± 33.557 µg/mL × min and 6.950 ± 0.45 µg/mL compared to 364.536 ± 45.215 µg/mL × min and 2.650 ± 0.55 µg/mL for the oral FLT suspension. With these promising findings, we conclude that encapsulation of FLT in cholesterol-loaded nanovesicles enhanced its anticancer activity and oral bioavailability which endorse its use in the management of prostate cancer.

Complete Genome Sequence of White Spot Syndrome Virus Isolated from Indian White Prawn (Fenneropenaeus indicus) in Egypt.

White spot disease, caused by the white spot syndrome virus (WSSV), has caused major losses in shrimp farming in Egypt since 2009. The genome sequence of the WSSV-Egypt isolate will be valuable in epidemiological studies to delineate the origin and spread of WSSV in Egypt and elsewhere in the world.

Complete Genome Sequences of Four Major Viruses Infecting Marine Shrimp in Egypt.

The genome sequences of four economically important shrimp viruses, Penaeus stylirostris densovirus 1, hepatopancreatic parvovirus, yellow head virus, and gill-associated virus, are reported here. Genome data are fundamental for epidemiological studies in determining the origins of these viruses detected for the first time in Egypt and in developing disease management strategies.

Evaluation of dysphagia in different phenotypes of early and idiopathic Parkinsonism.

BACKGROUND: Parkinsonism (PD) is a common neurodegenerative disorders into which dysphagia occurs mainly in the late stage and to a lesser extent in an early stage. Diagnosis of dysphagia particularly in early idiopathic Parkinson's disease (IPD) is important as dysphagia affects the quality of life of patients and most of the patients are unaware of this important symptom. METHOD: Fifty-four patients were enrolled in this study presented with early IPD attending to the outpatient clinic of Sohag University Hospital. All PD patients were assessed by using Unified Parkinson's Disease Rating Scale (UPDRS) and modified Hoehn and Yahr scale. IPD patients were classified into tremor dominant (TD) and postural instability/gait disorder (PIGD) phenotypes. Swallowing disturbance questionnaire (SDQ) and fiberoptic endoscopic evaluation of swallowing (FEES) were used to evaluate dysphagia. RESULTS: Thirty-five percent of patients experienced dysphagia when the patients were questioned, and this percent rises to 40% on using FEES. The results of SDQ were significantly correlated to the results of more accurate FEES. The percentage of dysphagia was higher in patients with PIGD than TD phenotype. Dysphagia was significantly associated with the mean of the Mini-Mental State Examination (MMSE), UPDRS, and modified Hoehn and Yahr scale. CONCLUSIONS: Dysphagia is a prevalent symptom in early IPD and significantly correlated with Parkinsonism phenotype, UPDRS, and modified Hoehn and Yahr scale.

Enhancing the Therapeutic Efficacy of Tamoxifen Citrate Loaded Span-Based Nano-Vesicles on Human Breast Adenocarcinoma Cells.

Serious adverse effects and low selectivity to cancer cells are the main obstacles of long term therapy with Tamoxifen (Tmx). This study aimed to develop Tmx-loaded span-based nano-vesicles for delivery to malignant tissues with maximum efficacy. The effect of three variables on vesicle size (Y1), zeta potential (Y2), entrapment efficiency (Y3) and the cumulative percent release after 24 h (Y4) were optimized using Box-Behnken design. The optimized formula was prepared and tested for its stability in different storage conditions. The observed values for the optimized formula were 310.2 nm, - 42.09 mV, 75.45 and 71.70% for Y1, Y2, Y3, and Y4, respectively. The examination using electron microscopy confirmed the formation of rounded vesicles with distinctive bilayer structure. Moreover, the cytotoxic activity of the optimized formula on both breast cancer cells (MCF-7) and normal cells (BHK) showed enhanced selectivity (9.4 folds) on cancerous cells with IC50 values 4.7 ± 1.5 and 44.3 ± 1.3 µg/ml on cancer and normal cells, respectively. While, free Tmx exhibited lower selectivity (2.5 folds) than optimized nano-vesicles on cancer cells with IC50 values of 9.0 ± 1.1 µg/ml and 22.5 ± 5.3 µg/ml on MCF-7 and BHK cells, respectively. The promising prepared vesicular system, with greater efficacy and selectivity, provides a marvelous tool to overcome breast cancer treatment challenges.

Primary Endovascular Treatment of Acute Ischemic Stroke Using Stent Retrievers: Initial Egyptian Experience.

BACKGROUND: Several mechanical thrombectomy (MT) devices have been designed with the goal of improving the recanalization rates of major intracranial artery occlusions. OBJECTIVE: In this single-center experience, we analyzed the acute ischemic stroke (AIS) treatment with Primary MT; safety and efficacy and clinical results in our patients with large vessel occlusion (LVO). METHODS: During a five-year period (from September 2011 to July 2016), out of 996 patients who presented to our center with a diagnosis of AIS, 113 (11.4%) patients (55 men and 58 women) underwent primary mechanical recanalization within three hours from onset of signs and symptoms for anterior and 12 hours for posterior circulation (with computer tomography angiography/perfusion ELVO). Successful recanalization (thrombolysis in cerebral infarction 2b-3), good outcome (modified Rankin scale score 0-2) and overall mortality rate, and symptomatic intracranial hemorrhage [sICH: parenchymal hematoma Type 1 or Type 2; National Institutes of Health Stroke Scale (NIHSS) score increment ≥4 points] were prospectively assessed. RESULTS: The mean age of the patients was 62 ± 11.73 years, with a baseline mean admission NIHSS score of 16.7 ± 3.2. The mean time from onset to puncture (time to treatment) was 208.55 ± 53.49. Successful recanalization was achieved in 104 (92%) cases. Good outcome was observed in 89 (78.8%) patients, and mortality was 11.5% (n = 13). sICH occurred in five (4.4%) patients. CONCLUSION: MT, within the first 4.5 hours, as primary treatment of acute LVO stroke provides high rate of recanalization and favorable clinical outcomes with low procedural complications.