PRE-FORMULATION STUDY ON 5-FLUOROURACIL AND CERTAIN LIPIDS FOR SOLID LIPID NANOPARTICLES PREPARATION

Objective: The study's objective involved compatibility studies to investigate the possible interactions between 5-fluorouracil (5-FU) and four different lipids, and the most appropriate lipid was chosen.  Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier Transform Infrared spectroscopy (FT-IR) are used for the compatibility study between 5-FU and several excipients as cholesterol, compritol®, stearic acid, and glycerol monostearate (GMS). Methods: The physical mixture between 5-FU and each lipid was made by mixing of a certain amount of drug with the same amount of lipid. Drug lipid blended mixtures were made by solvent evaporation casting method. 5-FU alone, physical mixture and blended mixture were measured using Differential scanning calorimetry (DSC) to investigate melting peak of drug and effect of each lipid on this melting point, X-ray diffraction (XRD) to observe the crystalline or amorphous state of drug and Fourier Transform Infrared (FT-IR) to determine any chemical interaction between drug and these lipids by observing any shift happened to characteristic peaks related to the drug. Results: 5-FU Tm (280.04 °C) peak appeared in drug-lipid physical mixtures with minor changes in position while this peak disappeared in 5-FU-compritol® and 5-FU-cholesterol blended mixture, indicating that the drug is molecular dispersed. XRD result showed that the crystalline structure of 5-FU was present in physical mixtures with four lipids, while in the 5-FU-compritol® blended mixture, the crystalline state of the drug was disappeared, confirming the DSC result. The FT-IR spectrum of the 5-FU-physical mixtures with four lipids showed that all characteristic peaks of the drug appeared with minor changes. In the case of 5-FU-blended mixtures with mentioned lipids, no chemical interaction occurred between the drug and mentioned lipids except in the drug-stearic acid blended mixture, the N-H peak at 3136.25 cm-1 was disappeared due to amide ester formation. Conclusion: The most appropriate lipids suitable for the preparation of 5-FU solid lipid nanoparticles were GMS and cholesterol

Immunohistochemical Expression of “c-MET” in Breast Carcinomas

BACKGROUND: Targeted therapies achieved great success in managing breast cancer, however, triple negative breast cancers (TNBCs) lack the expression of traditional therapeutic targets, and other subtypes develop resistance to current therapies. The c-MET receptor emerged as a potential target with well documented pro-proliferative pro-motility downstream signals and wide network of crosstalk with other effectors. Some reports describe a preferential expression of c-MET in TNBCs and promising results in early anti-c-MET clinical trials. However, the main cause of failure of these trials was attributed to patient selection. AIM: The objectives of the study were to assessment of c-MET in subtypes of breast cancer and its association with other clinicopathological variables that may predict its expression and possibly establish other rationales to refine patient selection for clinical trials. MATERIALS AND METHODS: Retrospective immunohistochemical study assessing c-MET (clone SP44) in 55 cases of breast carcinoma. The expression of c-MET> 5% was considered positive. RESULTS: c-MET was detected in 42% of cases. A statistically significant association of c-MET with extremes of age, advanced prognostic stage, carcinoma with medullary features, and high tumor infiltrating lymphocytes (TILs) was observed for the first time in our study. Grade III, hormone receptor negativity and TNBCs were also significantly associated with c-MET. Only negative progesterone receptor (PR) and high TILs were independently associated with c-MET in a multivariate analysis (p < 0.05). No significant association between c-MET and multifocality, size, node status, anatomic stage, lymphovascular or perineural invasion, and Ki-67 expression. CONCLUSION: PR negativity and high TILs might be useful c-MET predictors and selection tools for clinical trials but further studies are needed to validate the unprecedented findings which may not only aid in patient selection but may also inspire new paradigms in future studies

Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition

Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help prevent HF development and progression. Therapeutic attempts to prevent excessive post-MI inflammation in patients have included pharmacological interventions ranging from broad immunosuppression to immunomodulatory approaches targeting specific cell types or factors with the aim to maintain beneficial aspects of the early post-MI immune response. These include the blockade of early initiators of inflammation including reactive oxygen species and complement, inhibition of mast cell degranulation and leucocyte infiltration, blockade of inflammatory cytokines, and inhibition of adaptive B and T-lymphocytes. Herein, we provide a systematic review on post-MI immunomodulation trials and a meta-analysis of studies targeting the inflammatory cytokine Interleukin-1. Despite an enormous effort into a significant number of clinical trials on a variety of targets, a striking heterogeneity in study population, timing and type of treatment, and highly variable endpoints limits the possibility for meaningful meta-analyses. To conclude, we highlight critical considerations for future studies including (i) the therapeutic window of opportunity, (ii) immunological effects of routine post-MI medication, (iii) stratification of the highly diverse post-MI patient population, (iv) the potential benefits of combining immunomodulatory with regenerative therapies, and at last (v) the potential side effects of immunotherapies

Assessment of Ceruloplasmin, Hemopexin, and Haptoglobin in Asthmatic Children

BACKGROUND: Ceruloplasmin (Cp), haptoglobin, and hemopexin play a role in iron homeostasis and may function to modulate the systemic inflammatory response and be involved in tissue repair. We hypothesized that these proteins could be biological markers for bronchial asthma that reflect the involvement of iron oxidative stress in asthma pathogenesis. AIM: Evaluation of serum levels of proteins involved in iron homeostasis (Cp, hemopexin, and haptoglobin) in asthmatic children and their correlation to pulmonary functions. MATERIALS AND METHODS: Sixty moderate to severe persistent asthmatic children aged 6–13 years were included (30 during attacks and 30 in-between attacks). Thirty healthy matched controls were also recruited. All children were subjected to history taking, clinical evaluation and assessment of complete blood picture, serum levels of Cp, haptoglobin, hemopexin, and total IgE. Pulmonary function tests were assessed for all patients. RESULTS: Serum Cp and haptoglobin were significantly elevated in asthmatic children between attacks (448.04 ± 386.79), (993.33 ± 554.56) compared to controls (168.42 ± 13.46), (473.33 ± 350.3), (p = 0.0002, p < 0.0001) and to asthmatics during exacerbations (288.8 ± 219.6), (620 ± 467.86), (p = 0.014, p = 0.006). Serum hemopexin was significantly higher in asthmatics between attacks (509.33 ± 341.51) compared to controls (296.67 ± 158.38) (p < 0.003) but no significant difference compared to acute exacerbations (477.33 ± 396.6). No significant correlations were found between any of the assessed protein levels and pulmonary functions. Hemoglobin concentration was significantly higher among stable asthmatics compared to acute exacerbation and control groups. CONCLUSION: Cp, haptoglobin, and hemopexin can be used as a panel of non-invasive biomarkers that reflect the involvement of iron oxidative stress in asthma pathogenesis

3-(Adamantan-1-yl)-4-(prop-2-en-1-yl)-1H-1,2,4-triazole-5(4H)-thione

The title mol­ecule, C15H21N3S, exists as the thione tautomer in the solid state. The 1,2,4-triazole ring is almost planar (r.m.s. deviation = 0.004 Å) and the prop-2-en-1-yl chain is close to being perpendicular to this plane [C—N—C—C torsion angle = 77.1 (5)°]. In the crystal, centrosymmetric dimeric aggregates are formed by pairs of N—H⋯S hydrogen bonds as parts of eight-membered (⋯HNCS)2 synthons. These are connected into layers parallel to (101) via C—H⋯π inter­actions, where the π-system is the triazole ring. The investigated sample was a nonmerohedral twin; the refined domain ratio was 0.655 (4):0.345 (4)

MORPHOLOGICAL AND MOLECULAR CHARACTERIZATION OF ECTOMYCORRHIZAL FUNGI ISOLATED FROM EGYPTIAN ENVIRONMENT

In a trial to isolate and identify ectomycorrhi-zal fungi for the first time in Egypt 13 sporocarpes associated with rang of plants grown on Egyptian soils were collected, to be used for this purpose. Fungal isolates were obtained from collected spo-rocarpes and tested for ectomycorrhiza formation with Bauhinia sp. and Pinus seedlings. The paper sandwich technique was used for simultaneous inoculation of root apices Bauhinia to produce synchronously developing ectomycorrhizas. Typi-cal ectomycorrhizal roots were obtained within 14 days after inoculation with the collected strains. The isolates tested for ectomycorrhiza formation with Pinus sp. to ensure their identity by for-mation of distinct root characteristics on this host. Root colonization levels varied markedly among the tested fungal strains with respect to growth enhancement and NPK uptake of Pinus shoots and roots

Role of calcium and magnesium on dramatic physiological and anatomical responses in tomato plants

Minerals are the fundamental source of nutrients for plant functions such as photosynthesis, ATP currency, cellular respiration, metabolic activities, defense mechanisms, and tolerance to biotic and abiotic stressors. Minerals are the most significant component of plant nutrition and applying these minerals supplements can increase fruit output. The study’s main aim was to make agricultural farming easier by foliar applying newly created nutrients like Lebosol-calcium and Magnesium. The four treatments: To (Control), T1 (Lebosol-Mg-Plus, 3 ml/L), T2 (Lebosol-Ca-Forte, 3 ml/L), and T3 (Lebosol-Mg-Plus and Lebosol-Ca-Forte, 3 ml/L) was applied as foliar spray to the seedlings of tomato. It was found that T3 substantially enhanced tomato’s morphological features and yield. The treatment T3 significantly increased total soluble protein, chlorophyll content, and antioxidant enzyme activity. Furthermore, the foliar application of T3 considerably improved phenolic and ascorbic acid contents. The general anatomical features of the leaf, stem, and roots of tomato were qualitatively affected by the treatments. Application of Lebosol-Ca provided the highest total thickness of lamina, number of vessel elements, total phloem area, chlorenchyma layer, total area of vessel elements, xylem ratio, and increased palisade layer thickness, vessel diameter. Furthermore, T3 treatment showed a diverse impact on the internal structure of tomato organs, with palisade and spongy parenchyma growing to maximum values and vessel diameters expanding. T3 had also posed remarkable alterations in morpho-physiological, biochemical, and anatomical aspects in tested plants

Archaeometric Study of the Historic Terrazzo Pavement of Prince Mohamed Ali Museum, Cairo, Egypt

This research will shed light on studying a terrazzo pavement in Prince Mohamed Ali Museum (the case study). The authors used visual inspection, stereo microscope, USB microscope, XRPD analysis, and SEM.EDX to identify its components, deterioration aspects and execution techniques. The XRPD and SEM.EDX results revealed that Portland cement was used in the three layers of terrazzo because of the detection of Hatrurite, Alite, Anorthite, Albite, Aragonite, etc. Many pigments were used in the topping terrazzo layer as; Goethite, Greenalite, Hematite, Azurite and Magnetite. The divider strips were made of brass alloy and the topping layer chips were prepared from basalt, marble and sea shells

Periprocedural bridging anticoagulation in patients with venous thromboembolism: A registry- based cohort study

BackgroundUse of bridging anticoagulation increases a patient’s bleeding risk without clear evidence of thrombotic prevention among warfarin- treated patients with atrial fibrillation. Contemporary use of bridging anticoagulation among warfarin- treated patients with venous thromboembolism (VTE) has not been studied.MethodsWe identified warfarin- treated patients with VTE who temporarily stopped warfarin for a surgical procedure between 2010 and 2018 at six health systems. Using the 2012 American College of Chest Physicians guideline, we assessed use of periprocedural bridging anticoagulation based on recurrent VTE risk. Recurrent VTE risk and 30- day outcomes (bleeding, thromboembolism, emergency department visit) were each assessed using logistic regression adjusted for multiple procedures per patient.ResultsDuring the study period, 789 warfarin- treated patients with VTE underwent 1529 procedures (median, 2; interquartile range, 1- 4). Unadjusted use of bridging anticoagulation was more common in patients at high risk for VTE recurrence (99/171, 57.9%) than for patients at moderate (515/1078, 47.8%) or low risk of recurrence (134/280, 47.86%). Bridging anticoagulation use was higher in high- risk patients compared with low- or moderate- risk patients in both unadjusted (P = .013) and patient- level cluster- adjusted analyses (P = .031). Adherence to American College of Chest Physicians guidelines in high- and low- risk patients did not change during the study period (odds ratio, 0.98 per year; 95% confidence interval, 0.91- 1.05). Adverse events were rare and not statistically different between the two treatment groups.ConclusionsBridging anticoagulation was commonly overused among low- risk patients and underused among high- risk patients treated with warfarin for VTE. Adverse events were rare and not different between the two treatment groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156139/2/jth14903_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156139/1/jth14903.pd