Vitamin D and vitamin B12 profiles in children with primary nocturnal enuresis, an analytical cross-sectional study.

PURPOSE: To outline the prevalence of vitamin D and vitamin B12 deficiencies in enuretic children. METHODS: An analytical descriptive study was conducted on enuretic children who were followed up at the outpatient clinic for nocturnal enuresis at the Children's Hospital, Cairo University. Sociodemographic and clinical data were recorded. The levels of vitamin D and vitamin B12 were assessed and correlated with the severity of enuresis. RESULTS: Two hundred and eighty-eight children were enrolled. Insufficiency of Vitamin D predominated (n = 139; 48.3%). Vitamin D deficiency was present in 31.3%, n = 90 and it was normal in 20.5%, n = 59). Vitamin B12 deficiency was observed in 25% of the studied children, n = 72). The one-sample Wilcoxon signed-rank test was significant for both vitamins (P value =0.001). Vitamin D showed a stronger inverse correlation with the number of enuresis episodes per day than vitamin B12 (-0.680 vs. -0.219 respectively). A cut-off of 13.7 ng/ml for vitamin D was detected, below which the child was predicted to have failed dry nights. Using multivariate logistic regression, higher vitamin D levels and behavioural treatment coexistence were significant protective factors for the absence of dry nights. CONCLUSION: Low levels of vitamin D and B12 were detected in children with primary nocturnal enuresis, which could be considered a burden on the clinical severity of enuresis.

What is already known on this topic?Children with Primary Nocturnal Enuresis may have vitamin D and vitamin B₁₂ abnormalities as deficienciesWhat does this study add?Vitamin D insufficiency may be the most prevalent vitamin D abnormality in children with primary nocturnal enuresis. Vitamin D insufficiency may be more common in children with severe enuresis than vitamin B₁₂ deficiency.How might this study affect research, practice, or policy?This study may invite further research to examine the possible use of vitamin D and vitamin B12 as potential adjuvant therapies for children with Primary Nocturnal Enuresis.

Improving the bioavailability and therapeutic efficacy of felodipine for the control of diabetes-associated atherosclerosis: In vitro and in vivo characterization.

Felodipine has proven to be effective as an atherosclerosis therapy because it increases blood flow to the vessel wall. However, the poor solubility, low bioavailability, and hepatic first-pass metabolism of oral felodipine compromise its therapeutic effectiveness. The study's goal is to create a nasal pH-sensitive hydrogel of felodipine-loaded invasomes (IPHFI) that will improve felodipine's release, permeation, bioavailability, and efficacy as a potential diabetes-associated atherosclerosis therapy. According to the pre-formulation study, the felodipine-loaded invasomes formulation composed of phospholipid (3%w/v), cholesterol (0.16%w/v), ethanol (3%v/v) and cineole (1%v/v) was chosen as the optimum formulation. The optimum formulation was characterized in vitro and then mixed with a mixture of chitosan and glyceryl monooleate to make the IPHFI formulation. The IPHFI formulation enhanced the release and permeation of felodipine by 2.99 and 3-fold, respectively. To assess the efficacy and bioavailability of the IPHFI formulation, it was studied in vivo using an experimental atherosclerosis rat model. Compared to oral free felodipine, the nasal administration of the IPHFI formulation increased the bioavailability by 3.37-fold and decreased the serum cholesterol, triglycerides, LDL, and calcification score by 1.56, 1.53, 1.80, and 1.18 ratios, respectively. Thus, nasal IPHFI formulation may represent a promising diabetes-associated atherosclerosis therapy.

Childhood asthma biomarkers including zinc: An exploratory cross-sectional study.

BACKGROUND: Childhood bronchial asthma (BA) is a chronic inflammatory respiratory disease. Nutritional conditions, including zinc deficiency, can affect such allergic disorders. AIM: To outline the difference in serum zinc levels between asthmatic children and healthy controls. METHODS: A cross-sectional study was carried out at Children's Hospital, Cairo University, investigating serum zinc levels in children with BA (n = 40) and healthy children (n = 21). Other markers included serum ferritin, iron, hemoglobin (Hb), and immunoglobulin E (IgE) levels. Independent t-tests and Mann-Whinny tests were used for comparisons. The Kruskal-Wallis test was applied to compare serum ferritin and IgE levels with regard to asthma severity. Spearman's rank correlation was performed to explore the relationship between serum ferritin levels and both iron and Hb levels in asthmatic children. RESULTS: Children with BA had higher levels of zinc, yet the difference was not significant (P = 0.115). Serum ferritin and IgE levels were significantly higher in asthmatic children (P = 0.006 and 0.001, respectively), yet their levels did not differ significantly by severity (P = 0.623 and 0.126, respectively). There was a nonsignificant weak correlation between serum ferritin levels and both serum iron and Hb levels. CONCLUSION: Serum zinc levels do not seem to differ between asthmatic children and healthy children. Serum ferritin levels may be a marker of asthma control. Serum IgE levels are not markers of asthma severity.

Functional candesartan loaded lipid nanoparticles for the control of diabetes-associated stroke: In vitro and in vivo studies.

Diabetes mellitus is a metabolic disease that raises the odds of developing stroke. Candesartan has been used to prevent stroke due to its inhibitory effects on blood pressure, angiogenesis, oxidative damage, and apoptosis. However, oral candesartan has very limited bioavailability and efficacy due to its weak solubility and slow release. The study aimed to develop a nasal formulation of candesartan-loaded liposomes containing ethanol and propylene glycol (CLEP) to improve candesartan's delivery, release, permeation, and efficacy as a potential diabetes-associated stroke treatment. Using design expert software, different CLEP formulations were prepared and evaluated in vitro to identify the optimum formulation, which. The selected optimum formulation composed of 3.3% phospholipid, 10% ethanol, and 15% propylene glycol significantly increased the release and permeation of candesartan relative to free candesartan by a factor of 1.52 and 1.47, respectively. The optimum formulation significantly reduced the infarction after stroke in rats; decreased flexion, spontaneous motor activity, and time spent in the target quadrant by 70%, 64.71%, and 92.31%, respectively, and enhanced grip strength by a ratio of 2.3. Therefore, nasal administration of the CLEP formulation could be a potential diabetes-associated stroke treatment.

Fabrication of 3D Printed, Core-and-Shell Implants as Controlled Release Systems for Local siRNA Delivery.

The development and clinical translation of small interfering RNA (siRNA) therapies remains challenging owing to their poor pharmacokinetics. 3D printing technology presents a great opportunity to fabricate personalized implants for local and sustained delivery of siRNA. Hydrogels can mimic the mechanical properties of tissues, avoiding the problems associated with rigid implants. Herein, a thermoresponsive composite hydrogel suitable for extrusion 3D-printing is formulated to fabricate controlled-release implants loaded with siRNA-Lipofectamine RNAiMAX complexes. A hydrogel matrix mainly composed of uncharged agarose to protect siRNA from decomplexation is selected. Additionally, pluronic F127 and gelatin are added to improve the printability, degradation, and cell adhesion to the implants. To avoid exposing siRNA to thermal stress during the printing process, a core-and-shell design is set up for the implants in which a core of siRNA-complexes loaded-pluronic F127 is printed without heat and enclosed with a shell comprising the thermoresponsive composite hydrogel. The release profile of siRNA-complexes is envisioned to be controlled by varying the printing patterns. The results reveal that the implants sustain siRNA release for one month. The intactness of the released siRNA-complexes is proven until the eighth day. Furthermore, by changing the printing patterns, the release profiles can be tailored.

Utilizing 4D Printing to Design Smart Gastroretentive, Esophageal, and Intravesical Drug Delivery Systems.

The breakthrough of 3D printing in biomedical research has paved the way for the next evolutionary step referred to as four dimensional (4D) printing. This new concept utilizes the time as the fourth dimension in addition to the x, y, and z axes with the idea to change the configuration of a printed construct with time usually in response to an external stimulus. This can be attained through the incorporation of smart materials or through a preset smart design. The 4D printed constructs may be designed to exhibit expandability, flexibility, self-folding, self-repair or deformability. This review focuses on 4D printed devices for gastroretentive, esophageal, and intravesical delivery. The currently unmet needs and challenges for these application sites are tried to be defined and reported on published solution concepts involving 4D printing. In addition, other promising application sites that may similarly benefit from 4D printing approaches such as tracheal and intrauterine drug delivery are proposed.

The effect of hyperventilation versus normoventilation on cerebral oxygenation using near infrared spectroscopy in children undergoing posterior fossa tumor resection: A randomized controlled cross-over trial.

BACKGROUND: This study aims to compare the effect of two different ventilation strategies on cerebral oxygenation in children undergoing posterior fossa tumor excision surgeries. METHODS: Children scheduled for posterior fossa tumor surgeries were enrolled in this randomized, double-blinded, controlled cross-over trial. After induction of general anesthesia and positioning, participants were randomized to have mild hyperventilation for 30 min (phase 1) followed by normal ventilation for another 30 min (phase2) (early hyperventilation group, n = 23), or normal ventilation for 30 min (phase 1) followed by hyperventilation for 30 min (phase 2) (early normoventilation group, n = 19). Our primary outcome was cerebral oxygenation, measured using near-infrared spectroscopy (NIRS). Other outcomes included the intracranial pressure (ICP), brain relaxation score at the end of phase 1, and frequency of nadir NIRS. RESULTS: Forty-two children were available for final per protocol analysis. The cerebral oxygenation decreased after the hyperventilation phase compared to the baseline values and the corresponding phases of normoventilation. The mean difference [95% confidence intervals (CI)] in cerebral oxygen saturation between the hyperventilation and normal ventilation readings was 13.45 ± 1.14% [11.14-15.76] and 11.47 ± 0.96% [11.14-15.76] in the left and right sides, respectively (p-values <0.0001). Both carryover and period effects were not significant. The ICP at the end of phase 1 did not differ between the two groups: 22.12 ± 3.75 mmHg vs. 23.26 ± 4.33, mean difference [95%CI]: -0.78 [-3.05 to 1.5], p = 0.49. Brain relaxation score was similar in the two groups. CONCLUSION: In children undergoing posterior fossa craniotomy, moderate hyperventilation reduced cerebral oxygenation without significant improvement of the surgical brain relaxation or the ICP.

Novel Bile Salt Stabilized Vesicles-Mediated Effective Topical Delivery of Diclofenac Sodium: A New Therapeutic Approach for Pain and Inflammation.

The oral delivery of diclofenac sodium (DNa), a non-steroidal analgesic, anti-inflammatory drug, is associated with various gastrointestinal side effects. The aim of the research was to appraise the potential of transdermal delivery of DNa using bilosomes as a vesicular carrier (BSVC) in inflamed paw edema. DNa-BSVCs were elaborated using a thin-film hydration technique and optimized using a 31.22 multilevel categoric design with Design Expert® software 10 software (Stat-Ease, Inc., Minneapolis, MI, USA). The effect of formulation variables on the physicochemical properties of BSVC, as well as the optimal formulation selection, was investigated. The BSVCs were evaluated for various parameters including entrapment efficiency (EE%), vesicle size (VS), zeta potential (ZP) and permeation studies. The optimized BSVC was characterized for in vitro release, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and incorporated into hydrogel base. The optimized DNa-BSVC gel effectiveness was assessed in vivo using carrageenan-induced paw edema animal model via cyclooxygenase 2 (COX-2), interleukin 6 (IL-6), Hemooxygenase 1 (HO-1) and nuclear factor-erythroid factor2-related factor 2 (Nfr-2) that potentiate anti-inflammatory and anti-oxidant activity coupled with histopathological investigation. The resulting vesicles presented VS from 120.4 ± 0.65 to 780.4 ± 0.99 nm, EE% from 61.7 ± 3.44 to 93.2 ± 2.21%, ZP from -23.8 ± 2.65 to -82.1 ± 12.63 mV and permeation from 582.9 ± 32.14 to 1350.2 ± 45.41 µg/cm2. The optimized BSVCs were nano-scaled spherical vesicles with non-overlapped bands of their constituents in the FTIR. Optimized formulation has superior skin permeability ex vivo approximately 2.5 times greater than DNa solution. Furthermore, histological investigation discovered that the formed BSVC had no skin irritating properties. It was found that DNa-BSVC gel suppressed changes in oxidative inflammatory mediators (COX-2), IL-6 and consequently enhanced Nrf2 and HO-1 levels. Moreover, reduction of percent of paw edema by about three-folds confirmed histopathological alterations. The results revealed that the optimized DNa-BSVC could be a promising transdermal drug delivery system to boost anti-inflammatory efficacy of DNa by enhancing the skin permeation of DNa and suppressing the inflammation of rat paw edema.

Antidepressant and Cardioprotective Effects of Self-Nanoemulsifying Self-Nanosuspension Loaded with Hypericum perforatum on Post-Myocardial Infarction Depression in Rats.

Hypericum perforatum (HP) is characterized by potent medicinal activity. However, the poor water solubility of many HP constituents limits their therapeutic effectiveness. Self-nanoemulsifying self-nanosuspension loaded with HP (HP.SNESNS) was formulated to improve the bioefficacy of HP. It was prepared using 10% triacetin, 57% Tween 20, and 33% PEG 400 and then incorporated with HP extract (100 mg/mL). HP.SNESNS demonstrated a bimodal size distribution (258.65 ± 29.35 and 9.08 ± 0.01 nm) corresponding to nanosuspension and nanoemulsion, respectively, a zeta potential of -8.03 mV, and an enhanced dissolution profile. Compared to the unformulated HP (100 mg/kg), HP.SNESNS significantly improved cardiac functions by decreasing the serum myocardial enzymes, nitric oxide (NO), and tumor necrosis factor- α (TNF-α) as well as restoring the heart tissue's normal architecture. Furthermore, it ameliorates anxiety, depressive-like behavior, and cognitive dysfunction by decreasing brain TNF-α, elevating neurotransmitters (norepinephrine and serotonin), and brain-derived neurotrophic factor (BDNF). In addition, HP.SNESNS augmented the immunohistochemical expression of cortical and hippocampal glial fibrillary acidic protein (GFAP) levels while downregulating the cortical Bcl-2-associated X protein (Bax) expression levels. Surprisingly, these protective activities were comparable to the HP (300 mg/kg). In conclusion, HP.SNESNS (100 mg/kg) exerted antidepressant and cardioprotective activities in the post-MI depression rat model.

Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies.

During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many of the FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro and remarkable efficacy against COVID-19 in clinical trials, no pharmaceutical products have yet been declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes for the treatment of depression, neuralgia, migraine prophylaxis, and eating disorders which are frequently reported symptoms in COVID-19 patients. Herein, the efficacy of eight frequently prescribed FDA-approved antidepressants on the inhibition of both SARS-CoV-2 and MERS-CoV was assessed. Additionally, the in vitro anti-SARS-CoV-2 and anti-MERS-CoV activities were evaluated. Furthermore, molecular docking studies have been performed for these drugs against the spike (S) and main protease (Mpro) pockets of both SARS-CoV-2 and MERS-CoV. Results showed that Amitriptyline, Imipramine, Paroxetine, and Sertraline had potential anti-viral activities. Our findings suggested that the aforementioned drugs deserve more in vitro and in vivo studies targeting COVID-19 especially for those patients suffering from depression.

Photodynamic therapy fortified with topical oleyl alcohol-based transethosomal 8-methoxypsoralen for ameliorating vitiligo: Optimization and clinical study.

Vitiligo is a common autoimmune skin disorder that is characterized by patchy depigmentation of the skin due to melanocytes and melanin loss. Herein, photodynamic therapy mediated 8-methoxypsoralen (8-MOP), has been used fortified with topical oleyl alcohol-based transethosomes; to overcome the poor solubility and adverse effects associated with 8-MOP oral delivery. A 23 factorial design was used to study the formulation variables. In vitro and ex-vivo characterization besides a clinical study were conducted to assess therapeutic efficacy of the formulation. Results revealed that transethosomes were superior to transfersomes regarding drug protection from degradation. The optimized transethosomal formulation, composed of 50 mg oleyl alcohol, 10 mg Tween 80® and 20% v/v ethanol, exhibited high entrapment efficiency (83.87 ± 4.1%) and drug loading (105.0 ± 0.2%). Moreover, it showed small vesicular size (265.0 ± 2.9 nm) and PDI (0.19). The formulation depicted core and shell structure, high deformability index (12.45 ± 0.7 mL/s) and high ex-vivo skin permeation. The topical application of the developed 8-MOP transethosomal gel enhanced the effect of NB UVB radiation in the treatment of vitiligo patients and exhibited no side effects. Hence, it can be used as a future strategy for delivering 8-MOP without the need of systemic application.

Scrutinizing the Feasibility of Nonionic Surfactants to Form Isotropic Bicelles of Curcumin: a Potential Antiviral Candidate Against COVID-19.

Investigating bicelles as an oral drug delivery system and exploiting their structural benefits can pave the way to formulate hydrophobic drugs and potentiate their activity. Herein, the ability of non-ionic surfactants (labrasol®, tween 80, cremophore EL and pluronic F127) to form curcumin loaded bicelles with phosphatidylcholine, utilizing a simple method, was investigated. Molecular docking was used to understand the mechanism of bicelles formation. The % transmittance and TEM exhibited bicelles formation with labrasol® and tween 80, while cremophor EL and pluronic F127 tended to form mixed micelles. The surfactant-based nanostructures significantly improved curcumin dissolution (99.2 ± 2.6% within 10 min in case of tween 80-based bicelles) compared to liposomes and curcumin suspension in non-sink conditions. The prepared formulations improved curcumin ex vivo permeation over liposomes and drug suspension. Further, the therapeutic antiviral activity of the formulated curcumin against SARS-CoV-2 was potentiated over drug suspension. Although both Labrasol® and tween 80 bicelles could form bicelles and enhance the oral delivery of curcumin when compared to liposomes and drug suspension, the mixed micelles formulations depicted superiority than bicelles formulations. Our findings provide promising formulations that can be utilized for further preclinical and clinical studies of curcumin as an antiviral therapy for COVID-19 patients. Graphical Abstract.

In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans.

The resistance of Candida albicans to azole drugs represents a great global challenge. This study investigates the potential fungicidal effects of atorvastatin (ATO) combinations with fluconazole (FLU), itraconazole (ITR), ketoconazole (KET) and voriconazole (VOR) against thirty-four multidrug-resistant (MDR) C. albicans using checkerboard and time-kill methods. Results showed that 94.12% of these isolates were MDR to ≥ two azole drugs, whereas 5.88% of them were susceptible to azole drugs. The tested isolates exhibited high resistance rates to FLU (58.82%), ITR (52.94%), VOR (47.06%) and KET (35.29%), whereas only three representative (8.82%) isolates were resistant to all tested azoles. Remarkably, the inhibition zones of these isolates were increased at least twofold with the presence of ATO, which interacted in a synergistic (FIC index ≤ 0.5) manner with tested azoles. In silico docking study of ATO and the four azole drugs were performed against the Lanosterol 14-alpha demethylase enzyme (ERG11) of C. albicans. Results showed that the mechanism of action of ATO against C. albicans is similar to that of azole compounds, with a docking score (-4.901) lower than azole drugs (≥5.0) due to the formation a single H-bond with Asp 225 and a pi-pi interaction with Thr 229. Importantly, ATO combinations with ITR, VOR and KET achieved fungicidal effects (≥ 3 Log10 cfu/ml reduction) against the representative isolates, whereas a fungistatic effect (≤ 3 Log10 cfu/ml reduction) was observed with FLU combination. Thus, the combination of ATO with azole drugs could be promising options for treating C. albicans infection.

Delineating a potent antiviral activity of Cuphea ignea extract loaded nano-formulation against SARS-CoV-2: In silico and in vitro studies.

The outbreak of coronavirus disease-2019, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a worldwide emerging crisis. Polyphenols are a class of herbal metabolites with a broad-spectrum antiviral activity. However, most polyphenols encounter limited efficacy due to their poor solubility and degradation in neutral and basic environments. Thus, the effectiveness of their pharmaceutical application is critically dependent on the delivery systems to overcome the aforementioned drawbacks. Herein, Polyphenols-rich Cuphea ignea extract was prepared and its constituents were identified and quantified. Molecular docking was conducted for 15 compounds in the extract against SARS-CoV-2 main protease, among which rutin, myricetin-3-O-rhamnoside and rosmarinic acid depicted the most promising antiviral activity. Further, a self-nanoemulsifying formulation, composed of 10% oleic acid, 40% tween 20 and propylene glycol 50%, was prepared to improve the solubility of the extract components and enable its concurrent delivery permitting combined potency. Upon dilution with aqueous phases, the formulation rapidly Formsnanoemulsion of good stability and excellent dissolution profile in acidic pH when compared to the crude extract. It inhibited SARS-CoV-2 completely in vitro at a concentration as low as 5.87 µg/mL presenting a promising antiviral remedy for SARS-CoV-2, which may be attributed to the possible synergism between the extract components.

FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2.

(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC50 of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.

Crown Ether Nanovesicles (Crownsomes) Repositioned Phenytoin for Healing of Corneal Ulcers.

Drug repositioning is an important drug development strategy as it saves the time and efforts exerted in drug discovery. Since reepithelization of the cornea is a critical problem, we envisioned that the anticonvulsant phenytoin sodium can promote reepithelization of corneal ulcers as it was repurposed for skin wound healing. Herein, our aim is to develop novel crown ether-based nanovesicles "Crownsomes" of phenytoin sodium for ocular delivery with minimal drug-induced irritation and enhanced efficacy owing to "host-guest" properties of crown ethers. Crownsomes were successfully fabricated using span-60 and 18-crown-6 and their size, morphology, polydispersity index, ζ potential, drug loading efficiency, conductivity, and drug release were characterized. Crownsomes exhibited favorable properties such as formation of spherical nanovesicles of 280 ± 18 nm and -26.10 ± 1.21 mV surface charges. Crownsomes depicted a high entrapment efficiency (77 ± 5%) with enhanced and controlled-release pattern of phenytoin sodium. The optimum crownsomes formulation ameliorated ex vivo corneal drug permeability (1.78-fold than drug suspension) through the corneal calcium extraction ability of 18-crown-6. In vivo study was conducted utilizing an alkali-induced corneal injury rabbit model. Clinical and histopathological examination confirmed that crownsomes exhibited better biocompatibility and minimal irritation due to complex formation and drug shielding. Further, they enhanced corneal healing, indicating their effectiveness as a novel drug delivery system for ocular diseases.

Drug repurposing of nitazoxanide: can it be an effective therapy for COVID-19?

BACKGROUND: The current outbreak of pandemic coronavirus disease 2019 (COVID-19) aggravates serious need for effective therapeutics. Over recent years, drug repurposing has been accomplished as an important opportunity in drug development as it shortens the time consumed for development, besides sparing the cost and the efforts exerted in the research and development process. The FDA-approved antiparasitic drug, nitazoxanide (NTZ), has been found to have antiviral activity against different viral infections such as coronaviruses, influenza, hepatitis C virus (HCV), hepatitis B virus (HBV), and other viruses signifying its potential as a broad spectrum antiviral drug. Moreover, it has been recently reported that NTZ exhibited in vitro inhibition of SARS-CoV-2 at a small micromolar concentration. Additionally, NTZ suppresses the production of cytokines emphasizing its potential to manage COVID-19-induced cytokine storm. Furthermore, the reported efficacy of NTZ to bronchodilate the extremely contracted airways can be beneficial in alleviating COVID-19-associated symptoms. SHORT CONCLUSION: All these findings, along with the high safety record of the drug, have gained our interest to urge conductance of clinical trials to assess the potential benefits of using it in COVID-19 patients. Thus, in this summarized article, we review the antiviral activities of NTZ and highlight its promising therapeutic actions that make the drug worth clinical trials.

Fabrication, optimization, and in vitro/in vivo evaluation of diclofenac epolamine flash tablet.

The objective of this work was to design a diclofenac epolamine (DE) flash tablets (FTs) intended to dissolve in the mouth saliva, thereby improving the DE bioavailability and reducing its first-pass liver metabolism. Design-Expert software was used to build a 31.22 full factorial design (12 runs). FTs were fabricated using lyophilization process. The dissolution response was selected to pick the optimized run. The results indicate that the optimized run (R1) showed the fastest drug dissolution (total dissolution in 12 min). The predicted run (Rp) showed a desirability of about 0.93. Differential scanning calorimetry(DSC) analysis results showed a decrease in the drug melting point of the R1 formulation. Fourier-transform infrared spectroscopy (FTIR) showed the compatibility of the drug with other components of formulation, X-ray powder diffraction (XRPD) analysis showed the evolution of the drug physical state from a crystalline to an amorphous form and scanning electron microscopy(SEM) divugled the disappearance of drug crystals in gelatin strands. The results of the pharmacokinetic study performed in 6 human volunteers evidenced an increase in the maximum DE concentration in plasma and, consequently, an increased bioavailability of the FT formulation as compared with a reference formulation(Fr). Concisely, the developed FTs (R1) showed promising results which could be able to enhance oral bioavailability, reduce the therapeutic dose of the drug, and abate of the complications accompanied with conventional dosage forms. Graphical abstract.

Diagnostic value of serum cytokeratin-18 in children with chronic liver disease.

AIM: This study aimed to assess the diagnostic value of serum cytokeratin-18 (CK-18) in children with chronic liver diseases (CLD) and correlate its serum level with liver histology and other liver biomarkers. METHODS: This study included two groups, the first group included children with CLD and the second group included healthy matched age and gender subjects as a control group, complete history and clinical examination, and serum CK-18 was measured using the sandwich enzyme-linked immunosorbent assay technique. RESULTS: Serum concentrations of CK-18 were significantly elevated in CLD patients with mean ± standard deviation (1070.63 ± 699.2 ng/mL) compared to healthy controls mean ± standard deviation (203.95 ± 83.57 ng/mL). CK-18 levels were associated with a change in hepatocyte and portal tract (P = 0.005) as it was elevated with cirrhosis and fibrosis stage (P = 0.02) as it was elevated with moderate and severe fibrosis than mild fibrosis, also it showed a gradual increase in accordance with child Pugh score. There was a positive correlation between CK-18 levels and Total IgG, paediatric end-stage liver disease score and model for end-stage liver disease scores, the best cutoff point of CK-18 was 624 ng/mL, with sensitivity 93.06%, specificity 62.5% and diagnostic accuracy 90.0% for detection of fibrosis. CONCLUSION: CK-18 could be used as a non-invasive diagnostic marker in children with CLD.