Mechanisms of penetration and diffusion of drugs and cosmetic actives across the human Stratum corneum.

Based on the structure of the Stratum corneum (SC) the potential penetration/diffusion pathways of drugs and cosmetic actives through the SC are presented and discussed. The well-known lipophilic pathway across the SC is presented and relevant examples are used to show that highly lipophilic molecules such as glucocorticoids, coenzyme Q10 etc. are accumulated in the SC and penetrate into the inner liquid like layer of the SC lipid bilayer by lateral diffusion. The diffusion into and across the SC of highly hydrophilic drugs and active substances such as urea, amino acids and peptides is still under discussion. Another diffusion pathway for the highly hydrophilic molecules via the corneocytes and the corneodesmosomes is presented and discussed, the corneocytary diffusion pathway.

Delivery of small hydrophilic molecules across the stratum corneum: Identification of model systems and parameters to study topical delivery of free amino acids.

Free amino acids (FAAs) constitute the largest component (∼40 %) of the so-called natural moisturizing factors of the skin. Their level declines in dry skin conditions and one strategy to overcome this problem may involve the topical delivery of FAAs through appropriate strategy. The objective of the present study was therefore to identify alternative skin models and study the corneocyte-water partition coefficients (KCOR/W) and permeation coefficient (KP) of 18 FAAs. The KCOR/W was studied using standard protocols and the permeation studies were conducted using Franz diffusion cell. The results indicate that the FAAs have high partitioning behavior to the corneocytes. The KCOR/W values of the human COR and that of pig ear skin were better correlated with each other than that of keratin isolated from chicken feathers. The presence of lipid in the stratum corneum (SC), initial concentration of the FAAs, and permeation enhancers affect the KCOR/W. The FAAs have low permeation into the SC which suggests the need for permeation enhancers in designing dosage form containing these compounds. Even though the investigated mathematical models show good prediction of the Kp values, better prediction could be obtained by considering factors such as the possible entrapment of the FAAs by the CORs.

In vivo and in vitro transdermal availability of Ibuprofen using novel solubility enhancing fluid nanosized carrier systems.

The objective of this study was to explore the benefits of transdermal drug delivery systems as an alternative option for patients who are unable to tolerate oral administration of drugs, such as ibuprofen (IB). To achieve this, nonionic surfactants and three cosolvents were employed to develop new microemulsions (MEs) that contained IB as nanocarriers. The aim was to enhance the solubility and bioavailability of the drug after transdermal administration. The MEs were characterised by droplet size, polydispersity index (PDI), and rheological properties. Furthermore, the flux of IB was evaluated by Franz diffusion cells using excised rat skin and in vivo bioavailability using rats. The results showed that the MEs had ideal viscosity and droplet size below 100 nm. Moreover, using the developed MEs, an improvement in the solubility (170 mg/mL) and flux through the rat skin (94.6 ± 8.0 µg/cm2.h) was achieved. In addition, IB demonstrated a maximum plasma level of 0.064 mg/mL after 8 h of transdermal administration in rats using the ME with an increase in the bioavailability of about 1.5 times in comparison to the commercial IB gel. In conclusion, the developed nonionic MEs containing IB can be ideal nanocarriers and promising formulations for the transdermal administration of IB.

Dermal and Transdermal Macromolecule Delivery Using Enhancer Molecules and Colloidal Carrier Systems - Part 2: Percutaneous Administration of Heparin.

INTRODUCTION: Heparin is a commonly used anti-coagulant administered either by intravenous or subcutaneous injection for a systemic effect or topically for the treatment of peripheral vascular disorders. OBJECTIVE: This study aimed to formulate heparin in non-ionic colloidal carrier systems (CCSs) having enhanced percutaneous absorption for systemic and topical administration. METHODS: Five CCSs were developed and characterized for their rheological properties, droplet size, and drug loading. The percutaneous absorption of heparin was evaluated in vitro using Franz diffusion cells with rats' skin and with the aid of a developed high-pressure chromatography method. Furthermore, the efficacy of two developed heparin CCSs was tested percutaneously in rats by measuring the response against the time in comparison to subcutaneous administration. RESULTS: The rheograms and droplet size measurements showed that the developed drug delivery systems have Newtonian properties with a droplet size between 109 and 460 nm. As much as 500 mg of heparin could be loaded in around 5 mL of CCS. Furthermore, using Franz diffusion cells, a diffusion rate of 19.216 ± 2.01 USP U/cm2.h could be achieved for heparin-loaded CCSs. Moreover, the estimated percutaneous in vivo relative bioavailability in comparison to subcutaneous administration could reflect that at least more than 50% of the drug passed through the skin. CONCLUSION: The developed novel non-toxic CCSs containing heparin can be good candidates for percutaneous administration as alternative delivery systems for subcutaneous and intravenous invasive administration.

Investigating the nanostructure of a CER[NP]/CER[AP]-based stratum corneum lipid matrix model: A combined neutron diffraction & molecular dynamics simulations approach.

The human skin provides a physiochemical and biological protective barrier due to the unique structure of its outermost layer known as the Stratum corneum. This layer consists of corneocytes and a multi-lamellar lipid matrix forming a composite, which is a major determining factor for the barrier function of the Stratum corneum. A substantiated understanding of this barrier is necessary, as controlled breaching or modulation of the same is also essential for various health and personal care applications such as topical drug delivery and cosmetics to a name few. In this study, we discuss the state-of-the-art of neutron diffraction techniques, using specifically deuterated lipids, combined with the information obtained from molecular models using molecular dynamics simulations, to understand the structure and barrier function of the Stratum corneum lipid matrix. As an example, the effect of ceramide concentration on a lipid lamella system consisting of CER[NP]/CER[AP]/Cholesterol/free fatty acid (deprotonated) is studied. This study demonstrates the usefulness of the combined approach of neutron diffraction and molecular dynamics simulations for effective analysis of the model systems created for the Stratum corneum lipid matrix. The optimization of force fields by comparison with experimental data is furthermore an important step in the direction of providing a predictive quality.

Epigenetically silenced apoptosis-associated tyrosine kinase (AATK) facilitates a decreased expression of Cyclin D1 and WEE1, phosphorylates TP53 and reduces cell proliferation in a kinase-dependent manner.

Silencing of the Apoptosis associated Tyrosine Kinase gene (AATK) has been described in cancer. In our study, we specifically investigated the epigenetic inactivation of AATK in pancreatic adenocarcinoma, lower grade glioma, lung, breast, head, and neck cancer. The resulting loss of AATK correlates with impaired patient survival. Inhibition of DNA methyltransferases (DNMTs) reactivated AATK in glioblastoma and pancreatic cancer. In contrast, epigenetic targeting via the CRISPR/dCas9 system with either EZH2 or DNMT3A inhibited the expression of AATK. Via large-scale kinomic profiling and kinase assays, we demonstrate that AATK acts a Ser/Thr kinase that phosphorylates TP53 at Ser366. Furthermore, whole transcriptome analyses and mass spectrometry associate AATK expression with the GO term 'regulation of cell proliferation'. The kinase activity of AATK in comparison to the kinase-dead mutant mediates a decreased expression of the key cell cycle regulators Cyclin D1 and WEE1. Moreover, growth suppression through AATK relies on its kinase activity. In conclusion, the Ser/Thr kinase AATK represses growth and phosphorylates TP53. Furthermore, expression of AATK was correlated with a better patient survival for different cancer entities. This data suggests that AATK acts as an epigenetically inactivated tumor suppressor gene.

Dermal and transdermal peptide delivery using enhancer molecules and colloidal carrier systems. Part V: Transdermal administration of insulin.

In this study, insulin was loaded into non-ionic colloidal carrier systems (CCS) to be used as nano-sized drug delivery systems for transdermal administration. The CCS were characterized for their rheological properties, droplet size and drug loading. Also, the transdermal flux of insulin was estimated using Franz diffusion cells through the epidermis and all the layers of the rats' skin. The efficacy of the administration of the CCS was assessed in vivo transdermally in rats. Based on the rheological properties and droplet size results, the formulated fluids were identified as nano-sized systems having an aqueous colloidal phase, where the hydrophilic peptide is located. Also, a flux of insulin as high as 0.119 ± 0.016 and 1.328 ± 0.047 iu/cm2.h through the rat's skin and epidermis, respectively, could be achieved using CCSIn2. Moreover, the monitoring of the blood sugar level over 6.5 h after a single transdermal administration of CCS exhibited a slight decrease. However, a significant drop in the blood sugar level was observed when they were administered once every two days over 10 days. The developed insulin-loaded CCS containing the penetration enhancer DMSO are nano-sized drug delivery systems and can induce a delayed therapeutic effect by repeating the administration.

Cerosomes as skin repairing agent: Mode of action studies with a model stratum corneum layer at liquid/air and liquid/solid interfaces.

The stratum corneum (SC) is the largest physical barrier of the human body. It protects against physical, chemical and biological damages, and avoids evaporation of water from the deepest skin layers. For its correct functioning, the homeostasis of the SC lipid matrix is fundamental. An alteration of the lipid matrix composition and in particular of its ceramide (CER) fraction can lead to the development of pathologies such as atopic dermatitis and psoriasis. Different studies showed that the direct replenishment of SC lipids on damaged skin had positive effects on the recovery of its barrier properties. In this work, cerosomes, i.e. liposomes composed of SC lipids, have been successfully prepared in order to investigate the mechanism of interaction with a model SC lipid matrix. The cerosomes contain CER[NP], D-CER[AP], stearic acid and cholesterol. In addition, hydrogenated soybean phospholipids have been added to one of the formulations leading to an increased stability at neutral pH. For the mode of action studies, monolayer models at the air-water interface and on solid support have been deployed. The results indicated that a strong interaction occurred between SC monolayers and the cerosomes. Since both systems were negatively charged, the driving force for the interaction must be based on the ability of CERs head groups to establish intermolecular hydrogen bonding networks that energetically prevailed against the electrostatic repulsion. This work proved for the first time the mode of action by which cerosomes exploit their function as skin barrier repairing agents on the SC.

Binding of boswellic acids to functional proteins of the SARS-CoV-2 virus: Bioinformatic studies.

Boswellic acids (BAs) have been shown to possess antiviral activity. Using bioinformatic methods, it was tested whether or not acetyl-11-keto-ß-boswellic acid (AKBA), 11-keto-ß-boswellic acid (KBA), ß-boswellic acid (BBA), and the phosphorylated active metabolite of Remdesivir® (RGS-P3) bind to functional proteins of SARS-CoV-2, that is, the replicase polyprotein P0DTD1, the spike glycoprotein P0DTC2, and the nucleoprotein P0DTC9. Using P0DTD1, AKBA and KBA showed micromolar binding affinity to the RNA-dependent RNA polymerase (RdRp) and to the main proteinase complex Mpro . Phosphorylated BAs even bond in the nanomolar range. Due to their positive and negative charges, BAs and RGS-P3 bond to corresponding negative and positive areas of the protein. BAs and RGS-P3 docked in the tunnel-like cavity of RdRp. BAs also docked into the elongated surface rim of viral Mpro . In both cases, binding occurred with active site amino acids in the lower micromolecular to upper nanomolar range. KBA, BBA, and RGS-P3 also bond to P0DTC2 and P0DTC9. The binding energies for BAs were in the range of -5.8 to -6.3 kcal/mol. RGS-P3 and BAs occluded the centrally located pore of the donut-like protein structure of P0DTC9 and, in the case of P0DTC2, RGS-P3 and BAs impacted the double-wing-like protein structure. The data of this bioinformatics study clearly show that BAs bind to three functional proteins of the SARS-CoV-2 virus responsible for adhesion and replication, as does RGS-P3, a drug on the market to treat this disease. The binding effectiveness of BAs can be increased through phosphate esterification. Whether or not BAs are druggable against the SARS-CoV-2 disease remains to be established.

Two- and Three-Dimensional Physical-Chemical Characterization of CER[AP]: A Study of Stereochemistry and Chain Symmetry.

The stratum corneum represents the first skin barrier against chemical and physical damage. These unique properties are based on its peculiar lipid composition with ceramides (CERs) as the main protagonists. In this study, the structural and chemical properties of the α-OH phytosphingosine [AP] CER class have been investigated. α-OH CERs are present in the stratum corneum in their d-forms; however, in most model systems the diastereomer mixture with the synthetically produced l-form is used. The d-form is well-known to form a hydrogen bonding network that helps to reduce the permeability of the lipid matrix, while the l-form does not show any hydrogen bonding network formation. In this paper, 2D (monolayers) and 3D (aqueous dispersions) models have been used to thoroughly study the physical-chemical behaviors of CER[AP] diastereomers taking into account how the symmetry of the chain pattern influences the behavior of the molecules. The chains of both diastereomers arrange in an oblique unit cell, but only the d-CER[AP] forms a supramolecular lattice (subgel phase) in both model systems. Interestingly, the chain pattern does not play any role in structure formation since the hydrogen bonding network dictates the packing properties. The 1:1 mixture of the diastereomers phase separates into two domains: one is composed of practically pure d-form and the other one is composed of a mixture of the l-form with a certain amount of d-form molecules.

Free amino acid contents of selected Ethiopian plant and fungi species: a search for alternative natural free amino acid sources for cosmeceutical applications.

Free amino acids (FAAs), the major constituents of the natural moisturizing factor (NMF), are very important for maintaining the moisture balance of human skin and their deficiency results in dry skin conditions. There is a great interest in the identification and use of nature-based sources of these molecules for such cosmeceutical applications. The objective of the present study was, therefore, to investigate the FAA contents of selected Ethiopian plant and fungi species; and select the best sources so as to use them for the stated purpose. About 59 different plant species and oyster mushroom were included in the study and the concentrations of 27 FAAs were analyzed. Each sample was collected, lyophilized, extracted using aqueous solvent, derivatized with Fluorenylmethoxycarbonyl chloride (Fmoc-Cl) prior to solid-phase extraction and quantified using Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC-ESI-MS/MS) system. All the 27 FAAs were detected in most of the samples. The dominant FAAs that are part of the NMF were found at sufficiently high concentration in the mushroom and some of the plants. This indicates that FAAs that could be included in the preparations for the management of dry skin condition can be obtained from a single natural resource and the use of these resources for the specified purpose have both economic and therapeutic advantage in addition to fulfilling customer needs.

Interferon Regulatory Factor 9 Promotes Lung Cancer Progression via Regulation of Versican.

Transcription factors can serve as links between tumor microenvironment signaling and oncogenesis. Interferon regulatory factor 9 (IRF9) is recruited and expressed upon interferon stimulation and is dependent on cofactors that exert in tumor-suppressing or oncogenic functions via the JAK-STAT pathway. IRF9 is frequently overexpressed in human lung cancer and is associated with decreased patient survival; however, the underlying mechanisms remain to be elucidated. Here, we used stably transduced lung adenocarcinoma cell lines (A549 and A427) to overexpress or knockdown IRF9. Overexpression led to increased oncogenic behavior in vitro, including enhanced proliferation and migration, whereas knockdown reduced these effects. These findings were confirmed in vivo using lung tumor xenografts in nude mice, and effects on both tumor growth and tumor mass were observed. Using RNA sequencing, we identified versican (VCAN) as a novel downstream target of IRF9. Indeed, IRF9 and VCAN expression levels were found to be correlated. We showed for the first time that IRF9 binds at a newly identified response element in the promoter region of VCAN to regulate its transcription. Using an siRNA approach, VCAN was found to enable the oncogenic properties (proliferation and migration) of IRF9 transduced cells, perhaps with CDKN1A involvement. The targeted inhibition of IRF9 in lung cancer could therefore be used as a new treatment option without multimodal interference in microenvironment JAK-STAT signaling.

Non-ionic surfactants as innovative skin penetration enhancers: insight in the mechanism of interaction with simple 2D stratum corneum model system.

Transdermal drug delivery is a passive diffusion process of an active compound through the skin which is affected by drug solubility in the multilamellar lipidic matrix of the stratum corneum (SC). Widely used non-ionic surfactants (NIS) can be added into transdermal formulations to enhance the penetration of drugs by influencing the packing of the stratum corneum lipidic matrix. Objective of our study was to analyse the interaction between selected NIS and a simple SC lipidic matrix model system using a variety of surface-sensitive techniques based on the application of Langmuir monolayers. In this work, the well-known surfactant Polysorbate 80 was compared with a modern surfactant Sucrose monolaurate. Infrared reflection-absorption spectroscopy (IRRAS) and epifluorescence microscopy provide information about the effects of those surfactants on the SC model system. Monolayer isotherms of the SC model mixture indicate a very stiff and well-packed layer, however, packing defects are evidenced in epifluorescence studies. The injection of the two NIS underneath the SC monolayers proved their potential to penetrate into the SC model at the air-water interface having a maximum insertion pressure (MIP) above the assumed lateral pressure of biological membranes. The NIS adsorbed preferentially into packing defects seen in epifluorescence microscopy studies with Sucrose monolaurate being more active than Polysorbate 80 in disordering the SC monolayer.

Structural characterization of plant glucosylceramides and the corresponding ceramides by UHPLC-LTQ-Orbitrap mass spectrometry.

Ceramides (CERs) play a major role in skin barrier function and direct replacement of depleted skin CERs, due to skin disorder or aging, has beneficial effects in improving skin barrier function and skin hydration. Though, plants are reliable source of CERs, absence of economical and effective method of hydrolysis to convert the dominant plant sphingolipid, glucosylceramides (GlcCERs), into CERs remains a challenge. This study aims at exploring alternative GlcCERs sources and chemical method of hydrolysis into CERs for dermal application. GlcCERs isolated from lupin bean (Lupinus albus), mung bean (Vigna radiate) and naked barley (Hordium vulgare) were identified using ultra high performance liquid chromatography hyphenated with atmospheric pressure chemical ionization - high resolution tandem mass spectrometer (UHPLC/APCI-HRMS/MS) and quantified with validated automated multiple development-high performance thin layer chromatography (AMD-HPTLC) method. Plant GlcCERs were hydrolyzed into CERs with mild acid hydrolysis (0.1 N HCl) after treating them with oxidizing agent, NaIO4, and reducing agent, NaBH4. GlcCERs with 4,8-sphingadienine, 8-sphingenine and 4-hydroxy-8-sphingenine sphingoid bases linked with C14 to C26 α-hydroxylated fatty acids (FAs) were identified. Single GlcCER (m/z 714.5520) was dominant in lupin and mung beans while five major GlcCERs species (m/z 714.5520, m/z 742.5829, m/z 770.6144, m/z 842.6719 and m/z 844.56875) were obtained from naked barley. The GlcCERs contents of the three plants were comparable. However, lupin bean contains predominantly (> 98 %) a single GlcCER (m/z 714.5520). Considering the affordability, GlcCER content and yield, lupin bean would be the preferred alternative commercial source of GlcCERs. CER species bearing 4,8-sphingadienine and 8-sphingenine sphingoid bases attached to C14 to 24 FAs were found after mild acid hydrolysis. CER species with m/z 552.4992 was the main component in the beans while CER with m/z 608.5613 was dominant in the naked barley. However, CERs with 4-hydroxy-8-sphingenine sphingoid base were not detected in UHPLC-HRMS/MS study suggesting that the method works for mainly GlcCERs carrying dihydroxy sphingoid bases. The method is economical and effective which potentiates the commercialization of plant CERs for dermal application.

Epigenetic Inactivation of the Tumor Suppressor IRX1 Occurs Frequently in Lung Adenocarcinoma and Its Silencing Is Associated with Impaired Prognosis.

Iroquois homeobox (IRX) encodes members of homeodomain containing genes which are involved in development and differentiation. Since it has been reported that the IRX1 gene is localized in a lung cancer susceptibility locus, the epigenetic regulation and function of IRX1 was investigated in lung carcinogenesis. We observed frequent hypermethylation of the IRX1 promoter in non-small cell lung cancer (NSCLC) compared to small cell lung cancer (SCLC). Aberrant IRX1 methylation was significantly correlated with reduced IRX1 expression. In normal lung samples, the IRX1 promoter showed lower median DNA methylation levels (<10%) compared to primary adenocarcinoma (ADC, 22%) and squamous cell carcinoma (SQCC, 14%). A significant hypermethylation and downregulation of IRX1 was detected in ADC and SQCC compared to matching normal lung samples (p < 0.0001). Low IRX1 expression was significantly correlated with impaired prognosis of ADC patients (p = 0.001). Reduced survival probability was also associated with higher IRX1 promoter methylation (p = 0.02). Inhibition of DNA methyltransferase (DNMT) activity reactivated IRX1 expression in human lung cancer cell lines. Induced DNMT3A and EZH2 expression was correlated with downregulation of IRX1. On the cellular level, IRX1 exhibits nuclear localization and expression of IRX1 induced fragmented nuclei in cancer cells. Localization of IRX1 and induction of aberrant nuclei were dependent on the presence of the homeobox of IRX1. By data mining, we showed that IRX1 is negatively correlated with oncogenic pathways and IRX1 expression induces the proapoptotic regulator BAX. In conclusion, we report that IRX1 expression is significantly associated with improved survival probability of ADC patients. IRX1 hypermethylation may serve as molecular biomarker for ADC diagnosis and prognosis. Our data suggest that IRX1 acts as an epigenetically regulated tumor suppressor in the pathogenesis of lung cancer.

Investigation of ex vivo Skin Penetration of Coenzyme Q10 from Microemulsions and Hydrophilic Cream.

INTRODUCTION: Coenzyme Q10 (CoQ10) has been widely used in topical and cosmeceutical products due to its cutaneous antioxidant and energizer effects. CoQ10 is found in a higher concentration in the epidermis compared to dermis. The epidermal level of CoQ10 can be reduced due to several factors such as skin UV irradiation and photoaging. Various dermal nano-formulations have been investigated to overcome the skin barrier and enhance the poor penetration of CoQ10. The nanocarriers are designed to target and concentrate the CoQ10 in the viable epidermis. Most of these studies, however, failed to show the depth and extent of penetration of CoQ10 from the various carrier systems. OBJECTIVE: The distribution of CoQ10 across the various skin layers has to be shown using skin slices representing the different skin layers. METHODS: To realize this objective, a sensitive and selective HPLC method was developed and validated for the quantification of CoQ10 in the different skin slices. The method applicability to skin penetration (using excised human skin) as well as stability studies was investigated using CoQ10-loaded lecithin-based microemulsion (ME) and hydrophilic cream formulations. RESULTS: It could be shown that the highest concentration of CoQ10 in the viable epidermis, the target skin layer for CoQ10, was observed after application of the CoQ10 in the hydrophilic cream. This cream contains 10% of 2-ethylhexyl laurate which works obviously as a penetration enhancer for CoQ10. In contrast, the penetration of CoQ10 was lower from the ME. Just in the deeper dermis, a certain amount of CoQ10 could be detected. CONCLUSIONS: The HPLC method quantified the trace quantities of the CoQ10 distributed across the various skin layers and, hence, can be used to investigate the skin penetration of CoQ10 from various dermal standard and nano-formulations.

State of the Art in Stratum Corneum Research. Part II: Hypothetical Stratum Corneum Lipid Matrix Models.

This review is the second part of a series which presents the state of the art in stratum corneum (SC) lipid matrix (LM) research in depth. In this part, the various hypothetical models which were developed to describe the structure and function of the SC LM as the skin's barrier will be discussed. New as well as a cumulative assortment of older results which change the view on the different models are considered to conclude how well the different models are holding up today. As a final conclusion, a model, factoring in as much of the known data as possible, is concluded, unifying the varying different models into one which can be developed further, as new results are found in the future. So far, the model is described with a single crystalline or gel-like phase with a certain amount of nanocrystallites of concentrated ceramides (CERs) and free fatty acids and more fluid nanodomains caused by a fluidizing effect of the cholesterol. These domains are dynamically resolved and reformed and do not impair the barrier function. The chain conformation is not completely clear yet; however, an equilibrium of fully extended and hairpin-folded CERs with ratios depending on the properties of each individual CER species is proposed as most likely. An overlapping middle layer as described for the tri-layer model in part I of this series would be present for both conformations. The macroscopic broad-narrow-broad layering, observed in electron micrographs, is explained by an external templating by the lipid envelope, and an internal templating by short and long lipid chains each preferentially show a homophilic association, forming thicker and thinner bilayers, respectively. The degree of influence of the very long ω-hydroxy-CERs is discussed as well.

Extraction and characterization of celluloses from various plant byproducts.

Celluloses were extracted from teff straw (TS), enset fiber (EF), sugarcane bagasse (SB) and coffee hull (CH) agro-industrial byproducts generated in large quantities in Ethiopia. The present study aimed to explore these plant byproducts as alternative sources of cellulose for potential industrial applications, using various eco-friendly chlorine-free treatment conditions to obtain an optimum cellulose extraction condition. The byproducts and the as-extracted celluloses were analyzed for chemical compositions, yield, chemical functionality, crystallinity, thermal stability and morphology. EF yielded the highest cellulose content (60.0%), whereas CH the least (35.5%). FTIR spectra and ESEM morphological studies of the celluloses indicated progressive removal of non-cellulosic constituents. XRD analyses showed EF cellulose had the highest crystallinity index (CrI) (85.56%), crystallite size (5.52 nm), and proportion of crystallite interior chains of 200 plane (0.629), exhibiting unique physicochemical properties. The byproducts and the as-extracted celluloses showed Cellulose Iß crystal lattice, while celluloses from EF and SB also displayed (partial) polymorphic transition into Cellulose II. TGA studies revealed enhanced stability of the as-extracted celluloses. On the basis of the physicochemical characteristics of the celluloses, all the byproducts studied could be considered as alternative sources of cellulose for potential value-added industrial applications.

Is this a blast? An illustrated practical review on peripheral blood smear examination in the paediatric patient.

The morphologic findings on a peripheral blood smear can provide important clues that help establish a diagnosis or guide the workup of many clinical disorders. Finding a blast - whether clinically expected or not - is one of the most impactful of such findings. Pathologists, clinical haematologists, technologists, and trainees in the medical field often feel the need to refer to an illustrated reference when encountering suspected blasts and blast-mimics. This article provides a practical concise resource that demonstrates the morphological features of the various types of blasts and illustrates the cytologic characteristics that help distinguish them from their benign mimickers in the paediatric population.