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1.
Clin Obes ; : e12674, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740496

ABSTRACT

Obesity is predicted to affect approximately one-quarter of children/adolescents in Saudi Arabia by 2030, but there is limited evidence regarding the perceptions, attitudes, behaviours, and barriers to effective obesity care for adolescents living with obesity (ALwO), caregivers of ALwO, and healthcare professionals (HCPs). We report data from 500 ALwO (aged 12-<18 years), 500 caregivers, and 200 HCPs surveyed in Saudi Arabia as part of the global, cross-sectional ACTION Teens study (NCT05013359). Nearly all respondents recognized that obesity has a strong impact on overall health (ALwO 88%; caregivers 85%; HCPs 90%). Most ALwO and caregivers were aware of the ALwO's obesity status (95% and 99%, respectively) and worried about weight impacting the ALwO's future health (both ≥99%), and social media was their most commonly used source of weight-management information (60% and 53%, respectively). Among ALwO and caregivers who had discussed weight with an HCP in the past year, most experienced ≥1 negative feeling following their most recent discussion (61% and 59%, respectively). Although 81% of HCPs felt motivated to help their ALwO patients lose weight, 57% believed weight loss was completely the ALwO's responsibility (compared with only 37% of ALwO and 35% of caregivers). This may reflect the finding that only 24% of HCPs had received advanced training in obesity/weight management after medical school. Overall, while respondents had similar perceptions of the impact of obesity, we found HCPs' attitudes towards weight loss were not aligned with those of ALwO and caregivers, suggesting a need for improved communication and obesity education.

2.
Microorganisms ; 11(12)2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38138042

ABSTRACT

Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are transmitted through the fecal-oral route. HAV outbreaks and one HEV outbreak have been reported in Egypt. However, the impact of HAV-HEV co-infection is not known. In this study, we assessed HEV markers in acute HAV-infected patients (n = 57) enrolled in Assiut University hospitals. We found that 36.8% of HAV-infected patients were also positive for HEV markers (anti-HEV IgM and HEV RNA), while 63.2% of the patients were HAV mono-infected. Demographic and clinical criteria were comparable in both HAV mono-infected patients and HAV-HEV co-infected patients. Although liver enzymes were not significantly different between the two groups, liver transaminases were higher in the co-infected patients. Six patients developed acute liver failure (ALF); five of them were HAV-HEV-co-infected patients. The relative risk of ALF development was 8.5 times higher in HAV-HEV co-infection compared to mono-infection. Three cases of ALF caused by HAV-HEV co-infection were reported in children (below 18 years) and two cases were reported in adults. All patients developed jaundice, coagulopathy, and encephalopathy; all were living in rural communities. In conclusion: HAV-HEV co-infection can be complicated by ALF. The risk of ALF development in HAV-infected patients is higher when coinfection with HEV is present.

3.
Sci Rep ; 13(1): 19887, 2023 11 14.
Article in English | MEDLINE | ID: mdl-37963988

ABSTRACT

Pelargonium graveolens L'Hér is an important species of genus Pelargonium with an economic value. The unique rose scent of its oil is used in perfume and cosmetic industry. The oil is characterized by the presence of citronellol, geraniol and rose oxide. Fresh aerial parts of P. graveolens at GC-MS analysis of four seasons revealed that autumn constituted the highest yield of the oil. For the first time, optimization of the yield of extracted oil of P. graveolens was performed employing 3-level Box-Behnken design using 3-factors. The GC-MS analysis of the essential oil was performed for the 17-runs. The optimized extraction of the oil was performed employing numerical optimization and studied for antimicrobial, Minimum Inhibitory Concentration (MIC) and biofilm inhibitory activities. The 3 factors followed rank (plant material amount > water volume > NaCl percent in water), in their magnitude of effect on increasing yield of the oil. Increasing the plant material amount increased the yield of the oil by 6-folds compared to NaCl percent in water. The optimized yield of oil (4 ml) was obtained from extraction criteria (150 g of plant, 750 ml of water and 3.585% (26.85 g) of NaCl). Computational docking was performed to overcome the multi-drug resistant Gram-negative bacilli targeting undecaprenyl pyrophosphate synthase (UPPS). The optimized oil exhibited a promising inhibitory activity against Gram-negative bacteria (K. pneumonia and P. aeruginosa) with significant antibiofilm action (P < 0.05). Moreover, it exerted a synergistic effect when combined with various antibiotics (Cefoxitin, Cloxacillin, Oxacillin and Vancomycin) against MRSA clinical strains.


Subject(s)
Anti-Infective Agents , Oils, Volatile , Pelargonium , Sodium Chloride , Oils, Volatile/pharmacology , Anti-Infective Agents/pharmacology , Water , Microbial Sensitivity Tests
4.
Pathogens ; 12(5)2023 May 08.
Article in English | MEDLINE | ID: mdl-37242358

ABSTRACT

Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients' age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections.

6.
Int J Biol Macromol ; 237: 124147, 2023 May 15.
Article in English | MEDLINE | ID: mdl-36965558

ABSTRACT

Alginate and gelatin are natural macromolecules used to formulate biocompatible drug delivery systems. Hydroxyapatite (HA) is an osteophilic ceramic used to prepare bone scaffolds. The current study aimed at preparing and characterizing HA, zinc-doped HA, and 5-fluorouracil(5-FU)-loaded alginate-gelatin-based hydrogel scaffolds using different crosslinking solutions. 5-FU incorporation efficiency, in-vitro drug release, antitumor bioassays, FTIR, X-ray-diffraction (XRD), High-Resolution Transmission, and Scanning-Electron Microscope (HR-TEM and SEM) studies were conducted. XRD showed the incorporation of Zn2+ into HA structure with a deformity in HA crystal lattice and inhibited crystal growth. FTIR-spectra represented the characteristic bands corresponding to HA structure. HR-TEM showed a decreased HA crystal size and rod-like crystallites that increased with increasing zinc content. Zn2+ content and 5-FU-loading caused significant effects on the scaffolds' thickness (p-value = 0.021 and 0.035, respectively). Burst 5-FU release within 10-15 min followed by 100 % release within 4 h was observed. Zinc content showed a significant positive effect on the cytotoxicity% of the blank and drug-loaded scaffolds. XRD and FTIR studies revealed that 5-FU was completely incorporated into the hydrogel with no chemical interaction. SEM-imaging showed interconnected pores and needle-shaped drug particles. The prepared formulations showed promising physico-chemical properties for targeted delivery of 5-FU in the form of biocompatible bone scaffolds.


Subject(s)
Durapatite , Gelatin , Durapatite/chemistry , Gelatin/chemistry , Zinc/chemistry , Alginates/chemistry , Hydrogels/chemistry , Fluorouracil , Tissue Scaffolds/chemistry
7.
Infection ; 51(4): 887-895, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36334256

ABSTRACT

PURPOSE: Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt. METHODOLOGY: Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson's disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A-E viruses, cytomegalovirus, Epstein-Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus. RESULTS: A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease. CONCLUSION: This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens.


Subject(s)
Adenoviridae Infections , Epstein-Barr Virus Infections , Hepatitis, Viral, Human , Jaundice , Massive Hepatic Necrosis , Child , Humans , Adult , Male , Adolescent , Young Adult , Middle Aged , Female , Egypt/epidemiology , Herpesvirus 4, Human , Hepatitis, Viral, Human/epidemiology , Jaundice/epidemiology , Jaundice/etiology , Adenoviridae
8.
AAPS PharmSciTech ; 23(7): 248, 2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36056201

ABSTRACT

This study aimed to formulate and optimize solid-dispersion of meloxicam (MX) employing response-surface-methodology (RSM). RSM allowed identification of the main effects and interactions between studied factors on MX dissolution and acceleration of the optimization process. 33 full factorial design with 27 different formulations was proposed. Effects of drug loading percentage (A), carriers' ratio (B), method of preparation (C), and their interactions on percent MX dissolved after 10 and 30 min (Q10min & Q30min) from fresh and stored samples were studied in distilled water. The considered levels were 2.5%, 5.0%, and 7.5% (factor A), three ratios of Soluplus®/Poloxamer-407 (factor B). Physical mixture (PM), fusion method (FM), and hot-melt-extrusion (HME) were considered factor (C). Stability studies were carried out for 3 months under stress conditions. The proposed optimization design was validated by 3-extra checkpoints formulations. The optimized formulation was selected via numerical optimization and investigated by DSC, XRD, PLM, and in vitro dissolution study. Results showed that HME technique gave the highest MX dissolution rate compared to other techniques (FM & PM). At constant level of factor (C), the amount of MX dissolved increased by decreasing MX loading and increasing Soluplus in carriers' ratio. Actual responses of the optimized formulation were in close consistency with predicted data. Amorphous form of MX in the optimized formulation was proved by DSC, XRD, and PLM. Selected factors and their levels of the optimization design were significantly valuable for demonstrating and adapting the expected formulation characteristics for rapid dissolution of MX (Q10min= 89.09%) from fresh and stored samples.


Subject(s)
Chemistry, Pharmaceutical , Hot Melt Extrusion Technology , Chemistry, Pharmaceutical/methods , Drug Compounding/methods , Drug Stability , Hot Temperature , Meloxicam , Solubility
9.
Eur J Pharmacol ; 927: 175066, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35643302

ABSTRACT

The phytochemical sulforaphane (SFN) has been studied for its potential anti-obesity effect, but neither its molecular targets nor its interaction with the antimalarial drug chloroquine (CQ) has been fully delineated. Therefore, high-fat diet (HFD) obese rats were randomly allocated into one of five groups and were left untreated or gavaged orally with SFN (0.5 or 1 mg/kg), CQ (5 mg/kg), or their combination (0.5/5 mg/kg) for six successive weeks to assess their potential interaction and the enrolled mechanisms. SFN effectively reduced the HFD-induced weight gain, blood glucose, and serum leptin levels, and improved lipid profile. On the molecular level, SFN inhibited the lipogenesis-related enzymes, namely sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in both liver and visceral white adipose tissue (vWAT) of HFD obese rats. SFN also turned off the inflammatory pathway conserved Janus kinase/signaling transducers and activators of transcription/suppressor of cytokine signaling (JAK-2/STAT-3/SOCS-3) in these tissues, as well as the inflammatory markers nuclear factor-kappa (NF-κ) B and interleukin (IL)-22 in serum. In contrast, SFN downregulated the gene expression of microRNA (miR-200a), while significantly increasing the autophagic parameters; viz., beclin-1, autophagy-related protein (ATG)-7, and microtubule-associated protein 2 light chain 3 (LC3-II) in both liver and vWAT. On most of the parameters mentioned above, treatment with CQ solely produced a satisfactory effect and intensified the low dose of SFN in the combination regimen. These findings demonstrated the beneficial effects of using CQ as an add-on anti-obesity medicine to SFN.


Subject(s)
Chloroquine , Diet, High-Fat , Isothiocyanates , Janus Kinase 2 , STAT3 Transcription Factor , Sulfoxides , Suppressor of Cytokine Signaling 3 Protein , Animals , Chloroquine/pharmacology , Isothiocyanates/pharmacology , Janus Kinase 2/metabolism , Liver/metabolism , Obesity/drug therapy , Obesity/etiology , Obesity/metabolism , Random Allocation , Rats , STAT3 Transcription Factor/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Sulfoxides/pharmacology , Suppressor of Cytokine Signaling 3 Protein/metabolism
10.
Clin Appl Thromb Hemost ; 28: 10760296221107889, 2022.
Article in English | MEDLINE | ID: mdl-35698744

ABSTRACT

AIM: Our study's objectives were to study the clinical and laboratory characteristics that may serve as biomarkers for predicting disease severity, IL-10 levels, and frequencies of different T cell subsets in comorbid COVID-19 patients. METHODS: Sixty-two hospitalized COVID-19 patients with comorbidities were assessed clinically and radiologically. Blood samples were collected to assess the T lymphocyte subsets by flow cytometry and IL-10 levels by ELISA. RESULTS: The most common comorbidities observed in COVID-19 patients were diabetes mellitus (DM), hypertension, and malignancies. Common symptoms and signs included fever, cough, dyspnea, fatigue, myalgia, and sore throat. CRP, ferritin, D dimer, LDH, urea, creatinine, and direct bilirubin were significantly increased in patients than controls. Lymphocyte count and CD4+ and CD8+ T-cells were significantly decreased in comorbid COVID-19 patients, and CD25 and CD45RA expression were increased. CD4+ and CD8+ regulatory T cells (Tregs) and IL-10 levels were significantly decreased in patients. CONCLUSIONS: Many parameters were found to be predictive of severity in the comorbid patients in our study. Significant reductions in the levels and activation of CD4+ and CD8+ T-cells were found. In addition, CD4+ and CD8+ Tregs were significant decreased in patients, probably pointing to a prominent role of CD8+ Tregs in dampening CD4+ T-cell activation.


Subject(s)
COVID-19 , T-Lymphocyte Subsets , CD8-Positive T-Lymphocytes , COVID-19/immunology , Comorbidity , Humans , Interleukin-10 , Lymphocyte Count , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory
11.
Mar Environ Res ; 179: 105687, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35752034

ABSTRACT

This study comparing the expected pollution status of phenol along with heavy metals in sediments of two economic regions on the Mediterranean Sea coast using equilibrium partitioning method (EPM) as well as exposure of fishermen and populations to these sediments through ingestion and skin contact while swimming. El-Dekhila (ED) and Abu Talat (AT) regions were different in sediment texture and pollution sources. The expected ecological hazards of phenol in the studied areas were carried out using the equilibrium partitioning method (EPM) by which the partition coefficient of organic carbon-water, KOC (logKOC> 0.95-3.49), octanol-water coefficient, KOW (logKOW> 1.46-1.48) and sediment/liquid partition coefficient, Kd (log Kd < 3) detected high availability amounts of phenol in seawater. Risk quotient (RQ) for phenol in ED region ranged from high to moderate risk, while for AT region was low risk (<0.1); whereas, RQ values of heavy metals in sediments of two studied areas reflected the overall low risk without human hazards (HQ & HI < 1). RQAcute and RQChronic values were above 1 for phenol and heavy metals (Cu and Zn) reflecting that fish were the most sensitive to them in the two regions. Interestingly, this current investigation predicts future contamination of the studied areas especially phenol contamination and its relationship to heavy metals using some reasonable information and allowing the managers to manage how they decide on and protect these two areas. Thus, there is a constant need to use relatively simple tools capable of ensuring protection objectives with a quantity of information with realistic feasibility.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Animals , China , Egypt , Environmental Monitoring , Geologic Sediments , Humans , Mediterranean Sea , Metals, Heavy/analysis , Phenol , Risk Assessment , Water , Water Pollutants, Chemical/analysis
12.
Sci Rep ; 12(1): 8829, 2022 05 25.
Article in English | MEDLINE | ID: mdl-35614139

ABSTRACT

To the best of our knowledge, there have been no phytochemical studies concerning the wild plant Leontodon hispidulus Boiss. (Asteraceae). Optimization of the green extraction process of the plant aerial parts, identification of main phenolic compounds, evaluation of antioxidant, anti-inflammatory and anticancer activities of the optimized extract have been carried out. HPLC-analysis was performed using 95% ethanolic extract. 3-Level Box-Behnken Design was applied for optimization of extraction yield and total phenolic content using 3-factors (ethanol/water ratio, material/solvent ratio and extraction time). Antioxidant, anticancer and anti-inflammatory activities were evaluated by ABTS-assay, prostate and cervical carcinoma human cell lines and carrageenan-induced rat paw edema model, respectively. HPLC-analysis showed the presence of quercetin, rutin, kaempferol, chlorogenic and ρ-coumaric acids. Increasing both ethanol/water ratio and material/solvent ratio decreased the yield, while, it increased by prolongation of the extraction time. High material/solvent ratio increased the phenolic content. The optimized extract showed high total phenolic content (104.18 µg/mg) using 201 ml of 74.5% ethanol/water at 72 h and good biological activities. Antioxidant activity was found to be 41.89 mg Trolox-equivalent/gm, with 80% free radicals inhibition. For anti-inflammatory activity, 100 mg/kg of the extract inhibited the edema in rats by 83.5% after 4 h of carrageenan injection as compared to 81.7% inhibition by indomethacin. Prostate carcinoma cell line was more sensitive to the anticancer activity of the extract than cervical carcinoma cell line (IC50 = 16.5 and 23 µg/ml, respectively). The developed extraction procedure proved to be efficient in enriching the extract with phenolic compounds with promising anticancer, anti-inflammatory and antioxidant activities.


Subject(s)
Asteraceae , Carcinoma , Animals , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Asteraceae/chemistry , Carrageenan/therapeutic use , Edema/chemically induced , Edema/drug therapy , Ethanol/adverse effects , Male , Phenols/analysis , Plant Extracts/chemistry , Rats , Solvents/adverse effects , Water
13.
Viruses ; 13(10)2021 10 06.
Article in English | MEDLINE | ID: mdl-34696438

ABSTRACT

Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Hepatitis C/drug therapy , Adult , Aged , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/physiopathology , Egypt/epidemiology , Female , Hepacivirus/metabolism , Hepacivirus/pathogenicity , Hepatitis C/complications , Hepatitis C/virology , Humans , Interleukin-13/analysis , Interleukin-13/blood , Liver Neoplasms/metabolism , Liver Neoplasms/physiopathology , Male , MicroRNAs/analysis , MicroRNAs/blood , MicroRNAs/therapeutic use , Middle Aged , Treatment Failure , Viral Load/methods , Vitamin D/analysis , Vitamin D/blood
14.
Environ Sci Pollut Res Int ; 28(44): 62703-62715, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34215984

ABSTRACT

Phytoremediation of eight metals in mangrove forests was investigated by focusing on Avicennia marina at three locations along the Egyptian Red Sea coast. Average concentrations of metals in sediment followed the sequence Fe > Mn > Zn > Pb > Cr > Cu > Ni, while Cd was below the detection limit. Metal pollution index and enrichment factor indicated contamination of sediment by Pb, Cu, and Mn. Translocation factors from roots to seeds and leaves were highest for Cd and Mn, respectively, while bioaccumulation factors showed the highest absorptivity of Ni by roots to seeds and leaves organs. The variety in metals mobility and bioaccumilation may be attributed to the physicochemical properties of metals that affect their solubility and bioavailability. Multivariable analysis indicated the contribution of water and sediment characteristics to metal absorption. The study presents that the integrating approach of water, sediment, and plants may be a cornerstone for better recognizing the mangrove environment.


Subject(s)
Avicennia , Metals, Heavy , Water Pollutants, Chemical , Environmental Monitoring , Geologic Sediments , Indian Ocean , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis
15.
AAPS PharmSciTech ; 22(4): 146, 2021 Apr 30.
Article in English | MEDLINE | ID: mdl-33929614

ABSTRACT

In vitro and in vivo studies of gliclazide (GLZ)-loaded freeze-dried alginate-gelatin (AL-GL) beads were carried out, aiming to modify its oral bioavailability. Crosslinked freeze-dried GLZ AL-GL beads (particle size: 1.5- and 3.0-mm) were prepared. In vitro evaluation of GLZ AL-GL beads included SEM, DSC, FT-IR, and release rate study in gradient media. In vivo study was single-dose (4 mg/kg), randomized, parallel-group design, two-treatment (T: test GLZ AL-GL beads and R: reference product Diamicron® 30-mg MR tablet) conducted in 96 healthy rats. Each group was subdivided into 2 sub-groups (G1 and G2) having different blood sampling schemes for up to 72 h. Assessment of level A in-vitro-in-vivo correlation (IVIVC) model was carried out. AL-GL beads successfully increased GLZ release rate compared to R. GLZ percent released (Q4h) was 109.34, 86.85, and 43.43% for 1.5-mm and 3.0-mm beads and R, respectively. DSC analysis confirmed the interaction of AL-GL via crosslinking. No chemical interaction of GLZ has occurred as proved by FT-IR. Relative bioavailability (T/R) for AUC0-∞ was 132.45% for G1 and 146.16% for G2. No significant differences between T and R in the primary pharmacokinetic parameters were determined. Tmax values were found to be earlier in the case of G1 than those of G2. A secondary absorption peak of GLZ was clearly detected in the case of R while its sharpness was minimized in T. High IVIVC was established, and hence, the proposed in vitro release model perfectly correlated with the in vivo study. The current study design might be a platform to enable panoramic view for GLZ variability in vivo.


Subject(s)
Drug Compounding/methods , Gliclazide/chemical synthesis , Gliclazide/pharmacokinetics , Particle Size , Animals , Drug Liberation/physiology , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacokinetics , In Vitro Techniques , Male , Rats , Rats, Wistar , Spectroscopy, Fourier Transform Infrared/methods
16.
Front Physiol ; 12: 649462, 2021.
Article in English | MEDLINE | ID: mdl-33833690

ABSTRACT

BACKGROUND: Few data are available about the role of herbal extract loaded nanoparticles as an alternative safe medicine for the management of a gastric ulcer. AIM: This work is targeted at exploring the physiological effects of pomegranate loaded nanoparticles (PLN) against an indomethacin IND-induced gastric ulcer and comparing the results with traditional pomegranate peel extract (PPE). METHODS: Twenty-four rats were equally distributed into four groups: control, IND-treated, PLN-treated, and PPE-treated groups. Gross examination of gastric mucosa, and the calculation of ulcer and inhibition indices were done. Serum malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin 2 (IL-2), IL-6, IL-10, gastric homogenate prostaglandin E2 (PGE2), and nitric oxide (NO) were estimated. Mucosal endothelial nitric oxide synthase (eNOS mRNA) expression was identified by qPCR. Histological and immuno-histochemical staining of Tumor necrosis factor-α (TNF-α) and eNOS of stomach mucosa were performed. RESULTS: In comparison with the control group, IND-treated rats showed visible multiple ulcers with ulcer index, serum MDA, IL-2 and IL-6 were elevated while IL-10, PGE2, NO, and eNOS mRNA expression were significantly reduced. Damaged surface epithelium with disrupted glandular architecture and heavy leucocyte infiltration of lamina propria was noticed. Immunohistochemical staining of stomach mucosa revealed marked increased TNF-α and reduced eNOS. Oral administration of PLN and PPE succeeded in improving the gross mucosal picture, and all biochemical, histological, and immunohistochemical alterations. CONCLUSION: Both PLN and PPE potently alleviated IND-induced gastric ulceration via increasing TAC, PGE2, NO, eNOS mRNA, and protein expression. However, the healing effect of PLN was obviously greater than PPE-treated rats.

17.
Adv Pharm Bull ; 11(1): 86-95, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33747855

ABSTRACT

Purpose: This study aimed to evaluate the biological and mechanical properties of the poly(methyl methacrylate) (PMMA) denture base material as a vehicle incorporating novel hydroxyapatite nanoparticles (HA-NP) loaded with metronidazole (MZ) drug. Methods: HA-NP was prepared via wet-chemical-method, characterized by XRD, SEM/EDX, TEM, Fourier-transform infrared spectroscopy (FTIR), as well as the measurement of surface area and pore-size distribution. Four drug delivery formulas were prepared in the form of discs (10 x 2 mm) as follows: F1 (MZ/ HA-NP/PMMA), F2 (HA-NP/ PMMA), F3 (control-PMMA) and F4 (MZ/PMMA). Characterization of all formulas was performed using differential scanning calorimetry (DSC) and FTIR. MZ release rate, antimicrobial properties against three oral pathogens, cytotoxicity (MTT assay) and surface micro-hardness were also assessed. Statistical analysis of data was performed using one-way ANOVA test (P < 0.05). Results: DSC thermograms showed compatibility among MZ, HA-NP and PMMA along with physical stability over 6 months storage period at room temperature. FTIR spectroscopy proved the absence of any possible chemical interaction with MZ. MZ-HA-NP/PMMA formula showed relatively better drug release compared to MZ-PMMA. Both formulas showed statistically significant antimicrobial potentials against two microbial strains. MTT demonstrated reduction in cell cytotoxicity after 96 hours with the least value for HA-NP. Surface micro-hardness revealed non-significant reduction compared with the control PMMA. Conclusion: A novel biocompatible drug nanocarrier (HA-NP) was developed and incorporated in PMMA denture base material as a vehicle to allow prolonged sustained drug release to manage oral infections.

18.
Infect Drug Resist ; 14: 59-69, 2021.
Article in English | MEDLINE | ID: mdl-33469320

ABSTRACT

BACKGROUND: Hepatitis E virus (HEV) is an emerging infectious agent that causes acute hepatitis in developing and developed countries. Diagnosis of HEV infection has not been routinely done in Egyptian hospitals, and clinicians do not prescribe ribavirin (RBV) for acute hepatitis cases of unknown etiology (AHUE). We aimed to screen patients with AHUE for the presence of HEV markers and to determine the complications associated with HEV infection. PATIENTS AND METHODS: HEV markers (anti-HEV IgM, anti-HEV IgG, and HEV RNA) were assessed in patients with AHUE (n=300) admitted to Assiut University Hospitals. RT-qPCR was used to detect the viral load and sequencing analysis was carried out to determine the genotype of the detected viruses. Phylogenetic tree was constructed to evaluate the genetic relatedness between the isolates. Laboratory parameters and the outcomes of infection were determined. RESULTS: Acute HEV infection (AHE) was detected in 30 out of 300 (10%) of AHUE patients. Anti-HEV IgM, HEV RNA, and anti-HEV IgG were reported in 83%, 50%, and 43% of the samples, respectively. HEV RNA load ranged from 5×102 IU/mL to 1.1×104 IU/mL. Sequencing of the isolated viruses revealed that five viruses belong to HEV-1 and one isolate belongs to HEV-3 with high homology to the virus recently isolated from the cow and goat milk in the Egyptian villages. Although previous reports showed that attenuated HEV isolates were circulating in Egypt, four out of 30 patients (13%) developed coagulopathy and hepatic encephalopathy and died due to fulminant hepatic failure (FHF) within 3-6 weeks of hospitalization. Age, malignancy, and a history of pre-existing liver diseases were a risky factor for FHF development. CONCLUSION: AHE is common in Upper Egypt. Older patients with malignancy and/or a history of liver diseases are risky. HEV diagnosis and treatment become pivotal in Egyptian hospitals to reduce the fatality rate and they should start urgently and promptly.

19.
J Saudi Heart Assoc ; 32(4): 490-497, 2020.
Article in English | MEDLINE | ID: mdl-33537198

ABSTRACT

BACKGROUND: The relationship between glycemic control and the risk of cardiac disease in patients with Type 2 Diabetes Mellitus (T2DM) is controversial. 1,5-Anhydroglucitol (1,5-AG) is a biomarker of Glucose Variability (GV) and has been associated with clinical cardiovascular disease. However, its association with Subclinical Cardiac Disease (SCD) is unknown. AIM OF THE WORK: Study the association between GV and SCD. SUBJECTS AND METHODS: A cross-sectional study was conducted on 46 asymptomatic patients with T2DM as T2DM individuals group. Another 46 non-diabetic age and sex matched subjects were included as the healthy group. 1,5-AG was measured for all subjects. M-mode echocardiography in parasternal long axis view was used to measure Left Ventricular (LV) end diastolic dimension, LV end systolic dimension, ejection fraction, interventricular septum, LV posterior wall thickness, LV fractional shortening, left atrial dimension and aortic root dimension. Global Longitudinal Strain (GLS) was assessed by speckled tracking echocardiography. RESULTS: There were no significant differences between both groups as regarding age, sex, BMI, AST, ALT, and serum creatinine. 1,5-AG was lower in T2DM individuals group. As regarding the echo parameters no significant difference found between both groups regarding left ventricular, left atrial and aortic root dimensions. T2DM individuals group showed a statistically significant higher mitral valve area, apical 2 chambers, apical 4 chambers, apical longitudinal axis and GLS. No correlation found between HbA1c and any echo parameters while 1,5-AG showed a significantly negative correlation with apical 2 chambers, apical 4 chambers, apical longitudinal axis and GLS. ROC curve analysis detected 1,5-AG less than 7.51 ng/ml as the best cut off value with sensitivity of 85.7%, specificity 75% to diagnose patients with T2DM and SCD. CONCLUSION: 1,5-AG might be used as an additional surrogate marker to identify patients with T2DM and SCD.

20.
Drug Dev Ind Pharm ; 45(12): 1959-1972, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31692384

ABSTRACT

Objective: The aim of this study was to optimize the formulation of alginate-gelatin (AL-GL) beads containing gliclazide (GLZ) employing design of experiments (DOE).Significance: DOE enabled identification of the interaction between the studied factors, deep understanding of GLZ release pattern and acceleration of the optimization process.Methods: A three-factor, three-level face centered design was employed. The effects of GLZ content (GLZ%, X1), polymer ratio (AL:GL ratio, X2), crosslinker concentration (glutaraldehyde, GA%, X3), and their interaction on incorporation efficiency (IE) and release rate were studied. The optimized formulation was prepared using numerical optimization and evaluated by DSC, FT-IR, SEM and release rate studies.Results: Increasing GA% (X3) decreased IE (Y1) with the highest magnitude of effect among the studied factors. On the other hand, increasing alginate content in AL:GL ratio (X2) increased IE (Y1). The amount of GLZ released Q0.5h, Q2h(pH 1.2) and Q4h(pH 7.4) decreased by increasing GLZ% (X1) and AL:GL ratio (X2). Both drug content and AL:GL ratio appeared to affect water penetration into the gel matrix and drug release. Generally, there was a direct relationship between GA% (X3) and GLZ release in pH 1.2 (Q0.5h and Q2h). However, in pH 7.4 (Q4h), increasing GA% decreased GLZ release. In addition, increasing GA% caused deviation from zero-order release model. The actual responses of the optimized formulation were in close agreement with the predicted ones.Conclusion: The selected factors and their levels studied in the optimization design were useful for tailoring the anticipated formulation characteristics and GLZ release pattern.


Subject(s)
Chemistry, Pharmaceutical/methods , Drug Carriers/chemistry , Gliclazide/pharmacokinetics , Alginates/chemistry , Calorimetry, Differential Scanning , Cross-Linking Reagents/chemistry , Drug Liberation , Gelatin/chemistry , Gliclazide/administration & dosage , Hydrogen-Ion Concentration , Models, Chemical , Particle Size , Research Design , Solubility , Spectroscopy, Fourier Transform Infrared
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