Adjuvant role of corticosteroids in the treatment of community-acquired pneumonia

AbstractBackgroundDespite progress in life-support measures and antimicrobial therapy, the mortality of severe pneumonia has not varied since the mid-1990s, suggesting that other factors are of crucial importance in the evolution of this respiratory infection.ObjectiveTo evaluate the impact of hydrocortisone infusion in community-acquired pneumonia (CAP) in the attenuation of systemic inflammation and reduction of sepsis-related complications.MethodsThe study enrolled 80 patients, clinically and radiolodically diagnosed as community-acquired pneumonia, admitted to Chest department, Respiratory Intensive Care Unit, General Medicine Department and General Medicine Intensive Care Unit of Zagazig University Hospitals. Sixty of them were randomized to receive hydrocortisone as a bolus dose of 200mg intravenously once (only at day 1) then 10mg/h IV infusion for 7days and twenty received placebo, along with antibiotics according to IDSA/ATS 2007 guidelines which were given for both groups. The following parameters were compared in both groups; PaO2 and PaO2/FiO2 ratio, length of hospital stay, duration of IV antibiotic treatment, duration of mechanical ventilation, weaning success from mechanical ventilation, pneumonia complication and hospital outcome.ResultsHydrocortisone treated patients showed a significant improvement in PaO2 and PaO2/FiO2 ratio, a significant reduction in White blood cell count, C-reactive protein levels, Erythrocyte sedimentation rate, a significant reduction in the duration of mechanical ventilation, duration of IV antibiotic treatment, pneumonia complications, and length of hospital stay. Also there was an improvement of hospital outcome, weaning success from mechanical ventilation and radiological resolution compared to the placebo group.ConclusionAdjunctive 7day course of low dose hydrocortisone IV in patients with CAP hastens clinical recovery and prevents the development of sepsis-related complications with a significant reduction in the duration of mechanical ventilation, duration of IV antibiotics and length of hospital stay with the improvement in hospital outcome and weaning success from mechanical ventilation

Nature as a treasure trove of potential anti-SARS-CoV drug leads:a structural/mechanistic rationale

The novel Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a potential factor for fatal illness and a tremendous concern for global public health. The COVID-19 pandemic has entered a dangerous new phase. In the context of drug discovery, the structurally-unique and chemically-diverse natural products have been valuable sources for drug leads. In this review, we report for potential candidates derived from natural sources with well-reported in vitro efficacy against SARS-CoV during the last decade. Additionally, a library of 496 phenolic metabolites was subjected to a computer-aided virtual screening against the active site of the recently reported SARS-CoV Main protease (M(pro)). Analysis of physicochemical properties of these natural products has been carried out and presented for all the tested phenolic metabolites. Only three of the top candidates, viz. acetylglucopetunidin (31), isoxanthohumol (32) and ellagic acid (33), which are widely available in many edible fruits, obey both Lipinski's and Veber's rules of drug-likeness and thus possess high degrees of predicted bioavailability. These natural products are suggested as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics in the near future

Oral diclofenac potassium versus hyoscine-N-butyl bromide for pain relief during copper intrauterine device insertion: randomized clinical trial

Background: Present study was carried out to compare the analgesic effect of oral diclofenac potassium versus hyoscine-N-butyl bromide (HBB) for pain relief during copper intrauterine device (IUD) insertion.Methods: It was a a randomized clinical trial carried out at Assiut University Hospital, Assiut, Egypt. Parous women eligible for Copper IUD insertion were recruited and randomized in a 1:1 ratio to diclofenac potassium or HBB. The participants were asked to take 2 tablets of the study medications 30 minutes before IUD insertion. The primary outcome was the participant's self-rated pain perception using a 10-cm Visual Analogue Scale (VAS) during IUD insertion. We considered a 1.5 cm difference in VAS scores between study groups as clinically significant.Results: One hundred eight women were enrolled (n=54 in each group). Diclofenac significantly has lower mean pain score during speculum placement (1.73 vs. 2.13) and tenaculum placement (1.85 vs. 2.3) than HBB with p<0.001. No statistical significant differences between both groups in other steps of IUD insertion. Additionally, the duration of IUD insertion was significantly lower in the diclofenac group (5.34±0.76 vs. 5.74±1.23 minutes, p=0.045). No women reported side effects in both groups.Conclusions: The use of oral diclofenac potassium 30 minutes prior to copper IUD insertion slightly reduce the insertional pain and duration than oral HBB with no adverse effects

ANTIOXIDANT AND HEPATOPROTECTIVE EFFECTS OF JUSTICIA SPICIGERA ETHYL ACETATE FRACTION AND CHARACTERIZATION OF ITS ANTHOCYANIN CONTENT

Objective: The antioxidant and hepatoprotective activities of ethyl acetate (EA) fraction of the dried aerial part of Justicia spicigera were evaluated and the characterization of its anthocyanin content was done. Methods: Hepatic fibrosis was induced by carbon tetrachloride (CCl4) in rats. The ethyl acetate fraction was obtained by successive liquid/liquid fractionation of the crude cold ethanolic extract and the pigments were characterized by HPLC technique. The in vitro studies were carried out through evaluation of the EA fraction on the attenuation of 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals. The in vivo biological evaluation was done in CCl4 injured rats through determination of liver function indices, oxidative stress markers and the histopathological picture of the treated liver.Results: The phenolic content in the EA fraction was 42.94 mg/g. Twelve anthocyanins were identified, the major of which are peonidin 3, 5-diglucoside (64.30%), malvidin 3, 5-diglucoside (10.59%) and petunidin 3,5-diglucoside (4.71%). Treatment of CCl4 intoxicated rats with EA fraction recorded improvement in the liver function indices and oxidative stress markers. The histopathological observations confirmed our results.Conclusion: The ethyl acetate fraction of the dried aerial part of Justicia spicigera recorded antioxidant and hepato protective activities.Â

Contraception use among Muslim women in Alexandria, Egypt: a descriptive pilot study

Background: This pilot study aimed to create a questionnaire survey directed to understand knowledge gaps related to contraception among Muslim women in Alexandria, Egypt, so potential interventions could be designed to enable more informed decision-making. The project was a mixed-method, cross-sectional study using a questionnaire survey.Methods: Participants were randomly selected at outpatient clinics at Alexandria university hospitals in September and October 2020. The inclusion criteria were to be an 18 year old or older woman and able to give consent. The recruitment goal for this pilot study was 100 participants. The consented participants were interviewed about demographics, socio-structural and contraception use. The questionnaire was tested using a focus group of 11 women. The study data was collected using KoBoToolbox and exported to the SPSS software for descriptive analysis. The primary outcome was to validate the survey questionnaire and the secondary outcome to assess knowledge regarding contraception methods and emergency contraception.Results: The age of study participants ranged from 18-60 with a mean of 34 years. Almost all participants had previously heard of various contraceptive methods and 75% used them before. The majority did not know about emergency contraception. Most respondents had a favorable attitude toward family planning, and their primary sources of information were family and friends.Conclusions: Preliminary findings show that most women knew about contraception methods, though few of them heard of emergency contraception. Because of the patriarchal nature of Egyptian society, family planning education should target the whole population

Wound healing and antioxidant properties of <i>Launaea procumbens</i> supported by metabolomic profiling and molecular docking

Wounds adversely affect people’s quality of life and have psychological, social, and economic impacts. Herbal remedies of Launaea procumbens (LP) are used to treat wounds. In an excision wound model, topical application of LP significantly promoted wound closure (on day 14, LP-treated animals had the highest percentages of wound closure in comparison with the other groups, as the wound was entirely closed with a closure percentage of 100%, p < 0.05). Histological analysis revealed a considerable rise in the number of fibroblasts, the amount of collagen, and its cross-linking in LP-treated wounds. Gene expression patterns showed significant elevation of TGF-β levels (2.1-fold change after 7 days treatment and 2.7-fold change in 14 days treatment) and downregulation of the inflammatory TNF-α and IL-1β levels in LP-treated wounds. Regarding in vitro antioxidant activity, LP extract significantly diminished the formation of H(2)O(2) radical (IC(50) = 171.6 μg/mL) and scavenged the superoxide radical (IC(50) of 286.7 µg/mL), indicating antioxidant potential in a dose-dependent manner. Dereplication of the secondary metabolites using LC-HRMS resulted in the annotation of 16 metabolites. The identified compounds were docked against important wound-healing targets, including vascular endothelial growth factor (VEGF), collagen α-1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and transforming growth factor-β (TGF-β). Among dereplicated compounds, luteolin 8-C-glucoside (orientin) demonstrated binding potential to four investigated targets (VEGF, interleukin 1β, TNF-α, and collagen α-1). To conclude, Launaea procumbens extract could be regarded as a promising topical therapy to promote wound healing in excisional wounds, and luteolin 8-C-glucoside (orientin), one of its constituents, is a potential wound-healing drug lead

Discovery of two brominated oxindole alkaloids as staphylococcal DNA gyrase and pyruvate kinase inhibitors via inverse virtual screening

In the present study, a small marine-derived natural products library was assessed for antibacterial potential. Among 36 isolated compounds, a number of bis-indole derivatives exhibited growth-inhibitory activity towards Gram-positive strains (Bacillus subtilis and multidrug-resistant Staphylococcus aureus). 5- and 6-trisindoline (5-Tris and 6-Tris) were the most active derivatives (minimum inhibitory concentration, MIC, 4&ndash;8 &micro;M) that were subsequently selected for anti-biofilm activity evaluation. Only 5-Tris was able to inhibit the staphylococcal biofilm formation starting at a 5 &micro;M concentration. In order to investigate their possible molecular targets, both natural products were subjected to in silico inverse virtual screening. Among 20 target proteins, DNA gyrase and pyruvate kinase were the most likely to be involved in the observed antibacterial and anti-biofilm activities of both selected natural products. The in vitro validation and in silico binding mode studies revealed that 5-Tris could act as a dual enzyme inhibitor (IC50 11.4 &plusmn; 0.03 and 6.6 &plusmn; 0.05 &micro;M, respectively), while 6-Tris was a low micromolar gyrase-B inhibitor (IC50 2.1 &plusmn; 0.08 &micro;M), indicating that the bromine position plays a crucial role in the determination of the antibacterial lead compound inhibitory activity

Bioassay-guided isolation, metabolic profiling, and docking studies of hyaluronidase inhibitors from Ravenala madagascariensis

Hyaluronidase enzyme (HAase) has a role in the dissolution or disintegration of hyaluronic acid (HA) and in maintaining the heathy state of skin. Bioassay-guided fractionation of Ravenala madagascariensis (Sonn.) organ extracts (leaf, flower, stem, and root) testing for hyaluronidase inhibition was performed followed by metabolic profiling using LC&ndash;HRMS. Additionally, a hyaluronidase docking study was achieved using Molecular Operating Environment (MOE). Results showed that the crude hydroalcoholic (70% EtOH) extract of the leaves as well as its n-butanol (n-BuOH) partition showed higher HAase activity with 64.3% inhibition. Metabolic analysis of R. madagascariensis resulted in the identification of 19 phenolic compounds ranging from different chemical classes (flavone glycosides, flavonol glycosides, and flavanol aglycones). Bioassay-guided purification of the leaf n-BuOH partition led to the isolation of seven compounds that were identified as narcissin, rutin, epiafzelechin, epicatechin, isorhamnetin 7-O-glucoside, kaempferol, and isorhamnetin-7-O-rutinoside. The docking study showed that narcissin, rutin, and quercetin 3-O-glucoside all interact with HAase through hydrogen bonding with the Asp111, Gln271, and/or Glu113 residues. Our results highlight Ravenala madagascariensis and its flavonoids as promising hyaluronidase inhibitors in natural cosmetology preparations for skin care